Молекулярная биология, 2022, T. 56, № 5, стр. 732-750

Механизмы выживания опухолевых клеток, инфицированных цитомегаловирусом

Г. Р. Виноградская a*, А. В. Иванов b, А. А. Кущ c

a Петербургский институт ядерной физики им. Б.П. Константинова, Национальный исследовательский центр “Курчатовский институт”
188300 Гатчина, Ленинградская обл., Россия

b Институт молекулярной биологии им. В.А. Энгельгардта Российской академии наук
119991 Москва, Россия

c Национальный исследовательский центр эпидемиологии и микробиологии им. Н.Ф. Гамалеи Министерства здравоохранения Российской Федерации
123098 Москва, Россия

* E-mail: gvinogradskaya@mail.ru

Поступила в редакцию 28.03.2022
После доработки 19.04.2022
Принята к публикации 19.04.2022

Аннотация

Частое обнаружение ДНК и белков цитомегаловируса (ЦМВ) в злокачественных опухолях ставит вопрос об участии вируса в развитии онкологических заболеваний. Показано, что продукты генов ЦМВ могут регулировать процессы, связанные с ключевыми признаками рака. Роль ЦМВ как онкогенного фактора, способствующего злокачественной трансформации клеток, только начинает проясняться, однако его способность усиливать опухолевую прогрессию уже признается многими исследователями. В обзоре рассмотрена роль вирусных факторов, а также клеточных молекулярных путей, в устойчивости инфицированных ЦМВ опухолевых клеток к терапии. ЦМВ ингибирует апоптоз опухолевых клеток, что не только способствует опухолевой прогрессии, но и снижает чувствительность клеток к противоопухолевой терапии. Показано, что аутофагия может способствовать либо выживанию опухолевых клеток разного типа, либо их гибели. ЦМВ-инфекция при лейкозе индуцирует “защитную” аутофагию, которая подавляет апоптоз. Изучение роли вирусных факторов в формировании устойчивости опухолевых клеток к терапии и их взаимодействия с ключевыми путями гибели клеток необходимо для разработки средств, способных восстановить чувствительность опухолей к противоопухолевым препаратам.

Ключевые слова: цитомегаловирус, онкомодуляция, апоптоз, аутофагия, противоопухолевая терапия, резистентность к противоопухолевой терапии

Список литературы

  1. Cobbs C.S., Harkins L., Samanta M., Gillespie G.Y., Bharara S., King P.H., Nabors L.B., Cobbs C.G., Britt W.J. (2002) Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res. 62, 3347–3350.

  2. Samanta M., Harkins L., Klemm K., Britt W.J., Cobbs C.S. (2003) High prevalence of human cytomegalovirus in prostatic intraepithelial neoplasia and prostatic carcinoma. J. Urol. 170, 998–1002. https://doi.org/10.1097/01.ju.0000080263.46164.97

  3. Harkins L.E., Matlaf L.A., Soroceanu L., Klemm K., Britt W.J., Wang W., Bland K.I.,Cobbs C.S. (2010) Detection of human cytomegalovirus in normal and neoplastic breast epithelium. Herpesviridae. 1, 8. https://doi.org/10.1186/2042- 4280-1-8

  4. Taher C., de Boniface J., Mohammad A.A., Religa P., Hartman J., Yaiw K.C., Frisell J., Rahbar A., Söderberg-Naucler C. (2013) High prevalence of human cytomegalovirus proteins and nucleic acids in primary breast cancer and metastatic sentinel lymph nodes. PLoS One. 8, e56795. https://doi.org/10.1371/journal.pone.0056795

  5. Chen H.P., Chan Y.J. (2014) The oncomodulatory role of human cytomegalovirus in colorectal cancer: implications for clinical trials. Front. Oncol. 4, 314. https://doi.org/10.3389/fonc.2014.00314

  6. Paradowska E., Jabłońska A., Studzińska M., Wilczyński M., Wilczyński J.R. (2019) Detection and genotyping of CMV and HPV in tumors and fallopian tubes from epithelial ovarian cancer patients. Sci. Rep. 9, 19935. https://doi.org/10.1038/s41598-019-56448-1

  7. Athanasiou E., Gargalionis A.N., Boufidou F., Tsakris A. (2021) The association of human herpesviruses with malignant brain tumor pathology and therapy: two sides of a coin. Int. J. Mol. Sci. 22, 2250. https://doi.org/10.3390/ ijms22052250

  8. Touma J., Liu Y., Rahbar A., Pantalone M.R., Almazan N.M., Vetvik K., Söderberg-Naucler C., Geisler J., Sauer T. (2021) Detection of human cytomegalovirus proteins in paraffin-embedded breast cancer tissue specimens – a novel, automated immunohistochemical staining protocol. Microorganisms. 9, 1059. https://doi.org/10.3390/microorganisms905105

  9. Peredo-Harvey I., Rahbar A., Söderberg-Nauclér C. (2021) Presence of the human cytomegalovirus in glioblastomas-a systematic review. Cancers (Basel). 13, 5051. https://doi.org/10.3390/cancers13205051

  10. Soliman S.H.A., Orlacchio A., Verginelli F. (2021) Viral manipulation of the host epigenome as a driver of virus-induced oncogenes. Microorganisms. 9, 1179. https://doi.org/10.3390/microorganisms9061179

  11. Söderberg-Nauclér C. (2008) HCMV microinfections in inflammatory diseases and cancer. J. Clin. Virol. 41, 218–223.

  12. Cobbs C.S., Soroceanu L., Denham S., Zhang W., Kraus M.H. (2008) Modulation of oncogenic phenotype in human glioma cells by cytomegalovirus IE1-mediated mitogenicity. Cancer Res. 68, 724–730.

  13. Cobbs C.S. (2011) Evolving evidence implicates cytomegalovirus as a promoter of malignant glioma pathogenesis. Herpesviridae. 2, 10.

  14. Herbein G. (2018). The human cytomegalovirus, from oncomodulation to oncogenesis. Viruses. 10, E408. https://doi.org/10.3390/v10080408

  15. Söderberg-Nauclér C., Geisler J., Vetvik K. (2019) The emerging role of human cytomegalovirus infection in human carcinogenesis: a review of current evidence and potential therapeutic implications. Oncotarget. 10, 4333–4347.

  16. Blaylock R.I. (2019) Accelerated cancer aggressiveness by viral oncomodulation: new targets and newer natural treatments for cancer control and treatment. Surg. Neurol. Int. 10, 199. https://doi.org/10.25259/SNI_361_2019

  17. Baba R.E., Herbein G. (2021) Immune landscape of CMV infection in cancer patients: from “canonical” diseases toward virus-elicited oncomodulation. Front. Immunol. 12, 730765. https://doi.org/10.3389/fimmu.2021.730765

  18. Hanahan D., Weinberg R.A. (2000) The hallmarks of cancer. Cell. 100, 57–70. https://doi.org/10.1016/S0092- 8674(00)81683-9

  19. Hanahan D., Weinberg R.A. (2011) Hallmarks of cancer: the next generation. Cell. 144, 646–674. https://doi.org/10.1016/j.cell.2011.02.013

  20. Colotta F., Allavena P., Sica A., Garlanda C., Mantovani A. (2009) Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 30, 1073–1081. https://doi.org/10.1093/carcin/bgp127

  21. Flavahan W.A., Gaskell E., Bernstein B.E. (2017) Epigenetic plasticity and the hallmarks of cancer. Science. 357(6348), eaal2380. https://doi.org/10.1126/science.aal2380

  22. Senga S.S., Grose R.P. (2021) Hallmarks of cancer–the new testament. Open Biol. 11, 200358. https://doi.org/10.1098/rsob.20.035

  23. Seyfried T.N., Flores R.E., Poff A.M., D’Agostino D.P. (2014) Cancer as a metabolic disease: Implications for novel therapeutics. Carcinogenesis. 35, 515‒527.

  24. Seyfried T.N., Chinopoulos C. (2021) Can the mitochondrial metabolic theory explain better the origin and management of cancer than can the somatic mutation theory? Metabolites. 11, 572. https://doi.org/10.3390/metabo11090572

  25. Durah T., García-Romero N., Carrión-Navarro J., Madurga R., Mendivil A.O., Prat-Acin R., Garcia-Cañamaque L., Ayuso-Sacido A. (2021) Beyond the Warburg effect: oxidative and glycolytic phenotypes coexist within the metabolic heterogeneity of glioblastoma. Cells. 10, 202. https://doi.org/10.3390/cells10020202

  26. Chen X., Yi C., Yang M.J., Sun X., Liu X., Ma H., Li Y., Li H., Wang C., He Y., Chen G., Chen S., Yu L., Yu D. (2021) Metabolomics study reveals the potential evidence of metabolic reprogramming towards the Warburg effect in precancerous lesions. J. Cancer. 12, 1563–1574. eCollection, 2021https://doi.org/10.7150/jca.54252

  27. Vaupel P., Multhoff G. (2021) Revisiting the Warburg effect: historical dogma versus current understanding. J. Physiol. 599, 1745–1757. https://doi.org/10.1113/JP278810

  28. Munger J., Bajad S.U., Coller H.A., Shenk T., Rabinowitz J.D. (2006) Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathog. 2, e132.

  29. Yu Y., Clippinger A.J., Alwine J.C. (2011) Viral effects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection. Trends Microbiol. 19, 360–367. https://doi.org/10.1016/j.tim.2011.04.002

  30. Williamson C.D., DeBiasi R.L., Colberg-Poley A.M. (2012) Viral product trafficking to mitochondria, mechanisms and roles in pathogenesis. Infect. Disord. Drug Targets. 12, 18–37. https://doi.org/10.2174/187152612798994948

  31. DeBerardinis R.J., Chandel N.S. (2020) We need to talk about the Warburg effect. Nat. Metabolism. 2, 127–129.

  32. Vogelstein B., Papadopoulos N., Velculescu V.E., Zhou S., Diaz L.A. J., Kinzler K.W. (2013) Cancer genome landscapes. Science. 339(6127), 1546–1558. https://doi.org/10.1126/science.1235122

  33. Hui L., Chen Y. (2015) Tumor microenvironment: sanctuary of the devil. Cancer Lett. 368, 7–13. https://doi.org/10.1016/j.canlet.2015.07.039

  34. Bajaj J., Diaz E., Reya T.J. (2020) Stem cells in cancer initiation and progression. Cell Biol. 219, e201911053. https://doi.org/10.1083/jcb.201911053

  35. Alonso-Álvarez S., Colado E., Moro-García M.A., Alonso-Arias R. (2021) Cytomegalovirus in haematological tumours. Front. Immunol. 12, 703256. https://doi.org/10.3389/fimmu.2021.703256

  36. Soroceanu L., Matlaf L., Khan S., Akhavan A., Singer E., Bezrookove V., Decker S., Ghanny S., Hadaczek P., Bengtsson H., Ohlfestb J., Luciani-Torresa M.G., Harkinsf L., Perryg A., Guoc H., Soteropoulosc P., Charles S., Cobbs C.S. (2015) Cytomegalovirus immediate-early proteins promote stemness properties in glioblastoma. Cancer Res. 75, 3065–3076. https://doi.org/10.1158/0008-5472.CAN-14-3307

  37. Teo W.H., Chen H.P., Huang J.C., Chan Y.J. (2017) Human cytomegalovirus infection enhances cell proliferation, migration and upregulation of EMT markers in colorectal cancer-derived stem cell-like cells. Int. J. Oncol. 51, 1415–1426. https://doi.org/10.3892/ijo.2017.4135

  38. Li J.-W., Yang D. Yang D., Chen Z. Miao J, Liu W., Wang X., Qiu Z., Jin M., Shen Z. (2017) Tumors arise from the excessive repair of damaged stem cells. Med. Hypotheses. 102, 112–122. https://doi.org/10.1016/j.mehy.2017.03.005

  39. Zakaria S., Arakelyan A., Palomino R.A.Ñ., Fitzgerald W., Vanpouille C., Lebedeva A., Schmitt A., Bomsel M., Brittg W., Margolis L. (2018) Human cytomegalovirus-infected cells release extracellular vesicles that carry viral surface proteins. Virology. 524, 97–105.

  40. McSharry B.P., Avdic S., Slobedman B. (2012) Human cytomegalovirus encoded homologs of cytokines, chemokines and their receptors: roles in immunomodulation. Viruses. 4, 2448–2470. https://doi.org/10.3390/v4112448

  41. Fu M., Gao Y., Zhou Q., Zhang Q., Peng Y., Tian K., Wang J., Zheng X. (2014) Human cytomegalovirus latent infection alters the expression of cellular and viral microRNA. Gene. 536(2), 272–278.

  42. Buzdin A.A., Artcibasova A.V., Fedorova N.E., Suntsova M.V., Garazha A.V., Sorokin M.I., Allina D., Shalatonin M., Borisov N.M., Zhavoronkov A.A., Kovalchuk I., Kovalchuk O., Kushch A.A. (2016) Early stage of cytomegalovirus infection suppresses host microRNA expression regulation in human fibroblasts. Cell Cycle. 15, 3378–3389. https://doi.org/10.1080/15384101.2016.1241928

  43. Skaletskaya A., Bartle L.M., Chittenden T., A. Louise McCormick A.L., Mocarski E.S., Victor S. Goldmacher V.S. (2001) A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation. Proc. Nat. Acad. Sci. USA. 98, 7829–7834.

  44. Chiou S.H., Yang Y.P., Lin J.C., Hsu C.H., Jhang H.C., Yang Y.T., Lee C.H., Ho L.L., Hsu W.M., Ku H.H., Chen S.J., Chen S.S., Chang M.D., Wu C.W., Juan L.J. (2006) The immediate early 2 protein of human cytomegalovirus (HCMV) mediates the apoptotic control in HCMV retinitis through up-regulation of the cellular FLICE-inhibitory protein expression. J. Immunol. 177, 6199–6206. https://doi.org/10.4049/jimmunol.177.9.6199

  45. Baillie J., Sahlender D.A., Sinclair J.H. (2003) Human cytomegalovirus infection inhibits tumor necrosis factor alpha (TNF-α) signaling by targeting the 55-kilodalton TNF-α receptor. J. Virol. 77, 7007–7716.

  46. Bitra A., Nemcovicová I., Picarda G., Doukov T., Wang J., Chris A., Benedict C.A., Zajonc D.M. (2019) Structure of human cytomegalovirus UL144, an HVEM orthologue, bound to the B and T cell lymphocyte attenuator. J. Biol. Chem. 294, 10519–10529.

  47. Poole E., King C.A., Sinclair J.H., Alcami A. (2006) The UL144 gene product of human cytomegalovirus activates NFkB via a TRAF6-dependent mechanism. EMBO J. 25, 4390–4399.

  48. Andoniou C.E., Degli-Esposti M.A. (2006) Insights into the mechanisms of CMV-mediated interference with cellular apoptosis. Immun. Cell Biol. 84, 99–106.

  49. Cox M., Kartikasari A.E.R., Gorry P.R., Flanagan K.L., Plebanski M. (2021) Potential impact of human cytomegalovirus infection on immunity to ovarian tumours and cancer progression. Biomedicines. 9, 351. https://doi.org/10.3390/biomedicines9040351

  50. Craig R.R., Salcedo S.P., Gorvel J.-P.E. (2006) Pathogen–endoplasmic-reticulum interactions: in through the out door. Nat. Rev. Immunol. 6, 137–147.

  51. Johnson D.C., Hegde N.R. (2002) Inhibition of the MHC class II antigen presentation pathway by human cytomegalovirus. Curr. Top. Microbiol. Immunol. 269, 101–115.

  52. Johnsen J.I., Baryawno N., Söderberg-Nauclér C. (2011) Is human cytomegalovirus a target in cancer therapy? Oncotarget. 2, 1329–1338.

  53. Wilkinson G.W., Tomasec P., Stanton R.J., Armstrong M., Prod’homme V., Aicheler R., McSharry B.P., Rickardsa C.R., Cochrane D., Llewellyn-Lacey S., Wang E.C., Griffin C.A., Davison A.J. (2008) Modulation of natural killer cells by human cytomegalovirus. J. Clin. Virol. 41, 206–212.

  54. Berry R., Watson G.M., Jonjic S., Degli-Esposti M.A., Rossjohn J. (2020) Modulation of innate and adaptive immunity by cytomegaloviruses. Nat. Rev. Immunol. 20, 113–127. https://doi.org/10.1038/s41577-019-0225-5

  55. Dziurzynski K., Wei J., Qiao W., Hatiboglu M.A., Kong L.Y., Wu A., Wang Y., Cahill D., Levine N., Prabhu S., Rao G., Sawaya R., Heimberger A.B. (2011) Glioma-associated cytomegalovirus mediates subversion of the monocyte lineage to a tumor propagating phenotype. Clin. Cancer Res. 17, 4642–4649. https://doi.org/10.1158/1078-0432.CCR-11-0414

  56. Chinta P., Garcia E.C., Tajuddin K.H., Akhidenor N., Davis A., Faure L., Spencer J.V. (2020) Control of cytokines in latent cytomegalovirus infection. Pathogens. 9, 858. https://doi.org/10.3390/pathogens9100858

  57. Würstle M.L., Rehm M.A. (2014) Systems biology analysis of apoptosome formation and apoptosis execution supports allosteric procaspase-9 activation. J. Biol. Chem. 289, 26277–26289. https://doi.org/10.1074/jbc.M114.590034

  58. Hevlera J.F., Chiozzia R.Z., Cabrera-Oreficec A., Brandtc U., Arnoldc S., Hecka A.J.R. (2021) Molecular characterization of a complex of apoptosis-inducing factor 1 with cytochrome c oxidase of the mitochondrial respiratory chain. Proc. Natl. Acad. Sci. USA. 118, e2106950118. https://doi.org/10.1073/pnas.2106950118

  59. Laptenko O., Prives C. (2006) Transcriptional regulation by p53: one protein, many possibilities. Cell Death Differ. 13, 951–961. https://doi.org/10.1038/sj.cdd.4401916

  60. Geng Y., Walls K.C., Ghosh AP., Akhtar R.S., Klo-cke B.J., Roth K.A. (2010) Cytoplasmic p53 and activated Bax regulate p53-dependent, transcription-independent neural precursor cell apoptosis. J. Histochem. Cytochem. 58, 265–275. https://doi.org/10.1369/jhc.2009.954024

  61. Dadsena S., King L.E.,  García-Sáez A.J. (2021) Apoptosis regulation at the mitochondria membrane level. Biochim. Biophys. Acta Biomembranes. 1863, 183716. https://doi.org/10.1016/j.bbamem.2021.183716

  62. Bertini I., Chevance S., Del Conte R., Lalli D., Turano P. (2011) The anti-apoptotic Bcl-xL protein, a new piece in the puzzle of pytochrome C interactome. PLoS One. 6(4), e18329. https://doi.org/10.1371/journal.pone.0018329

  63. Singh R., Letai A., Sarosiek K. (2019) Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat. Rev. Mol. Cell. Biol. 20(3), 175–193. https://doi.org/10.1038/s41580-018-0089-8

  64. Kantari C., Walczak H. (2011) Caspase-8 and Bid: caught in the act between death receptors and mitochondria. Biochim. Biophys. Acta. 1813, 558–563. https://doi.org/10.1016/j.bbamcr.2011.01.026

  65. Song M., Bode A.M., Dong Z., Lee M.H. (2019) AKT as a therapeutic target for cancer. Cancer Res. 79, 1019–1031. https://doi.org/10.1158/0008-5472.CAN-18-2738

  66. Johnson R.A., Wang X., Ma X.L., Huong S.M., Huang E.S. (2001) Human cytomegalovirus upregulates the phosphatidylinositol 3-kinase (PI3-K) pathway: inhibition of PI3-K activity inhibits viral replication and virus-induced signaling. J. Virol. 75, 6022–6032. https://doi.org/10.1128/JVI.75.13.6022-6032.2001

  67. Yu Y., Alwine J.C. (2002) Human cytomegalovirus major immediate-early proteins and simian virus 40 large T antigen can inhibit apoptosis through activation of the phosphatidylinositide 3'-OH kinase pathway and the cellular kinase Akt. J. Virol. 76, 3731–3738. https://doi.org/10.1128/jvi.76.8.3731-3738.2002

  68. Cinatl J. Jr., Vogel J.U., Kotchetkov R., Doerr H.W. (2004) Oncomodulatory signals by regulatory proteins encoded by human cytomegalovirus: A novel role for viral infection in tumor progression. FEMS Microbiol. Rev. 28, 59–77. https://doi.org/10.1016/j.femsre.2003.07.005

  69. Kamada H., Nito C., Endo H., Chan P.H. (2007) Bad as a converging signaling molecule between survival PI3-K/Akt and death JNK in neurons after transient focal cerebral ischemia in rats. J. Cereb. Blood Flow Metab. 27, 521–533. https://doi.org/10.1038/sj.jcbfm.9600367

  70. Paulus C., Nevels M. (2009) The human cytomegalovirus major immediate-early proteins as antagonists of intrinsic and innate antiviral host responses. Viruses. 1, 760–779. https://doi.org/10.3390/v1030760

  71. Cinatl J.Jr., Cinatl J., Vogel J.U., Kotchetkov R., Driever P.H., Kabickova H., Kornhuber B., Schwa-be D., Doerr H.W. (1998) Persistent human cytomegalovirus infection induces drug resistance and alteration of programmed cell death in human neuroblastoma cells. Cancer Res. 58, 367‒372.

  72. Porta C., Paglino C., Mosca A. (2014) Targeting PI3K/ Akt/mTOR signaling in cancer. Front. Oncol. 4, 64. https://doi.org/10.3389/fonc.2014.00064

  73. Abbasi A., Forsberg K., Bischof F. (2015) The role of the ubiquitin-editing enzyme A20 in diseases of the central nervous system and other pathological processes. Front. Mol. Neurosci. 8, 21. https://doi.org/10.3389/fnmol.2015.00021

  74. Soroceanu L., Akhavan A., Cobbs C.S. (2008) Platelet-derived growth factor-alpha receptor activation is required for human cytomegalovirus infection. Nature. 455, 391–395. https://doi.org/10.1038/ nature07209

  75. Kabanova A., Marcandalli J., Zhou T., Bianchi S., Baxa U., Tsybovsky Y., Lilleri D., Silacci-Fregni C., Foglierini M., Fernandez-Rodriguez B.M., Druz A., Zhang B., Geiger R., Pagani M., Sallusto F., Kwong P.D., Corti D., Antonio Lanzavecchia A., Perez L. (2016) Platelet-derived growth factor-alpha receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer. Nat. Microbiol. 8, 16082. https://doi.org/10.1038/nmicrobiol.2016.82

  76. Lindsey S., Langhans S.A. (2015) Epidermal growth factor signaling in transformed cells. Int. Rev. Cell Mol. Biol. 314, 1–41. https://doi.org/10.1016/bs.ircmb.2014.10.001

  77. Buehler J., Zeltzer S., Reitsma J., Petrucelli A., Umashankar M., Rak M., Zagallo P., Schroeder J., Terhune S., Goodrum F. (2016) Opposing regulation of the EGF receptor: a molecular switch controlling cytomegalovirus latency and replication. PLoS Pathog. 12(5), e1005655. https://doi.org/10.1371/journal.ppat.1005655

  78. Goodrum F., Reeves M., Sinclair J., High K., Shenk T. (2007) Human cytomegalovirus sequences expressed in latently infected individuals promote a latent infection in vitro. Blood. 110, 937–945. https://doi.org/10. 1182/blood-2007-01-070078

  79. Cojohari O., Peppenelli M.A., Chan G.C. (2016) Human cytomegalovirus induces an atypical activation of Akt to stimulate the survival of short-lived monocytes. J. Virol. 90, 6443–6452. https://doi.org/10.1128/JVI.00214-16

  80. Mahmud J., Miller M.J., Altman A.M., Chan G.C. (2020) Human cytomegalovirus glycoprotein-initiated signaling mediates the aberrant activation of Akt. J. Virol. 94(16), e00167-20. https://doi.org/10.1128/JVI.00167-20

  81. Filippakis H., Spandidos D.A., Sourvinos G. (2010) Herpesviruses: hijacking the Ras signaling pathway. Biochim. Biophys. Acta. 1803, 777–785. https://doi.org/10.1016/j.bbamcr.2010.03.007

  82. Barbosa R., Acevedo L.A., Marmorstein R. (2021) The MEK/ERK network as a therapeutic target in human cancer. Mol. Cancer Res. 19, 361–374. https://doi.org/10.1158/1541-7786.MCR-20-0687

  83. Hancock M.H., Mitchell J., Goodrum F.D., Nelson J.A. (2020) Human cytomegalovirus miR-US5-2 downregulation of GAB1 regulates cellular proliferation and UL138 expression through modulation of epidermal growth factor receptor signaling pathways. mSphere. 5(4), e00582-20. https://doi.org/10.1128/mSphere.00582-20

  84. Maa J., Edlichb F., Bermejoa G.A., Norrisb K.L., Youleb R.J., Tjandraa N. (2012) Structural mechanism of Bax inhibition by cytomegalovirus protein vMIA. Proc. Natl. Acad. Sci. USA. 109, 20901–20906. www.pnas.org/cgi/doi/10.1073/pnas.1217094110

  85. Pauleau A.-L., Larochette N., Giordanetto F., Scholz S.R., Poncet D., Zamzami N., Goldmacher V.S., Kroemer G. (2007) Structure–function analysis of the interaction between Bax and the cytomegalovirus-encoded protein vMIA. Oncogene. 26, 7067–7080. https://doi.org/10.1038/sj.onc.1210511

  86. Reeves M.B., Davies A.A., McSharry B.P., Wilkinson G.W., Sinclair J.H. (2007) Complex I binding by a virally encoded RNA regulates mitochondria-induced cell death. Science. 316, 1345–1348. https://doi.org/10.1126/science.1142984

  87. Nogalski M.T., Solovyov A., Kulkarni A.S., Desai N., Oberstein A., Levine A.J., Ting D.T., Shenk T., Greenbaum B.D. (2019) A tumor-specific endogenous repetitive element is induced by herpesviruses. Nat. Commun. 10, 90. https://doi.org/10.1038/s41467-018-07944-x

  88. Tanne A., Muniz L.R., Puzio-Kuter A., Leonova K.I., Gudkov A.V., Ting D.T., Monasson R., Cocco S., Levine A.J., Bhardwaj N., Greenbaum B.D. (2015) Distinguishing the immunostimulatory properties of noncoding RNAs expressed in cancer cells. Proc. Natl. Acad. Sci. USA. 112, 15154–15159. https://doi.org/10.1073/pnas.1517584112

  89. Gottwein E., Cullen B.R. (2008) Viral and cellular micro RNAs as determinants of viral pathogenesis and immunity. Cell Host Microbe. 3, 375–387. https://doi.org/10.1016/j.chom.2008.05.002

  90. Deshpande R.P., Panigrahi M., Chandrasekhar Y.B.V.K., Babu P.P. (2018) Profiling of microRNAs modulating cytomegalovirus infection in astrocytoma patients. Neurol. Sci. 39, 1895–1902. https://doi.org/10.1007/s10072-018-3518-8

  91. Liang Q., Wang K., Wang B., Cai Q. (2017) HCMV-encoded miR-UL112-3p promotes glioblastoma progression via tumour suppressor candidate 3. Sci. Rep. 7, 44705.

  92. Zhang J., Huang Y., Wang Q., Ma Y., Qi Y., Liu Z., Deng J., Ruan Q. (2020) Levels of human cytomegalovirus miR-US25-1-5p and miR-UL112-3p in serum extracellular vesicles from infants with HCMV active infection are significantly correlated with liver damage. Eur. J. Clin. Microbiol. Infect. Dis. 39, 471–481. https://doi.org/10.1007/s10096-019-03747-0

  93. Stern-Ginossar N., Elefant N., Zimmermann A., Wolf D.G., Saleh N., Biton M., Horwitz E., Prokocimer Z., Prichard M., Hahn G., Goldman-Wohl D., Greenfield C., Yagel S., Hengel H., Altuvia Y., Marqalit H., Mandelboim O. (2007) Host immune system gene targeting by a viral miRNA. Science. 317, 376–381. https://doi.org/10.1126/science.1140956

  94. Babu S.G., Pandeya A., Verma N., Shukla N., Kumar R.V., Saxena S. (2014) Role of HCMV miR-UL70-3p and miR-UL148D in overcoming the cellular apoptosis. Mol. Cell. Biochem. 393, 89–98. https://doi.org/10.1007/s11010-014-2049-8

  95. Diggins N.L., Skalsky R.L., Hancock M.H. (2021) Regulation of latency and reactivation by human cytomegalovirus miRNAs. Pathogens. 10, 200. https://doi.org/10.3390/pathogens10020200

  96. Fu N.Y., Sukumaran S.K., Yu V.C. (2007) Inhibition of ubiquitin-mediated degradation of MOAP-1 by apoptotic stimuli promotes Bax function in mitochondria. Proc. Natl. Acad. Sci. USA. 104, 10051–10056. www.pnas.orgcgidoi10.1073pnas.0700007104

  97. Tan C.T. Zhou Q.-L., Su Y.-C., Fu N.Y. Chang H.-C., Tao R.N., Sukumaran S.K., Baksh S., Tan Y.-J., Sabapathy K., Yu C.-D., Yu V.C. (2016) MOAP-1 mediates Fas-induced apoptosis in liver by facilitating tBid recruitment to mitochondria. Cell Rept. 16, 174–185.

  98. Tan K.O., Fu N.Y., Sukumaran S.K., Chan S.L., Kang J.H., Chen B.S., Yu V.C. (2005) Map-1, is a mitochondrial effector of bax. Proc. Natl. Acad. Sci. USA. 50, 14623–14628.

  99. Monian P., Jiang X. (2012) Clearing the final hurdles to mitochondrial apoptosis: regulation post cytochrome C release. Exp. Oncol. 34, 185–191.

  100. Tabas I., Ron D. (2011) Integrating the mechanism of apoptosis induced by endoplasmic reticulum stress. Nat. Cell. Biol. 13, 184–190. https://doi.org/10.1038/ncb0311-184

  101. Zhang Y., Han C.Y., Duan F.G., Fan X.-X., Yao X.-J., Parks R.J., Tang Y.-J., Wang M.-F., Liu L., Tsang B.K., Leung E.L.-H. (2019) p53 sensitizes chemoresistant non-small cell lung cancer via elevation of reactive oxygen species and suppression of EGFR/PI3K/AKT signaling. Cancer Cell Int. 19, 188. doi.org/https://doi.org/10.1186/s12935-019-0910-2

  102. Hwang F.S., Zhang Z., Cai H., Huang D.Y., Huong S.M., Cha C.Y., Huang E.S. (2009) Human cytomegalovirus IE1-72 protein interacts with p53 and inhibits p53-dependent transactivation by a mechanism different from that of IE2-86 protein. J. Virol. 83, 12388–12398.

  103. Alexandrova E.M., Moll U.M. (2012) Role of p53 family members p73 and p63 in human hematological malignancies. Leuk. Lymphoma. 53, 2116–2129. https://doi.org/10.3109/10428194.2012.684348

  104. Rozenberg J.M., Zvereva S., Dalina A., Blatov I., Zubarev I., Luppov D., Bessmertnyi A., Romanishin A., Alsoulaiman L., Kumeiko V., Kagansky A., Melino G., Ganini C., Barlev N.A. (2021) The p53 family member p73 in the regulation of cell stress response. Biol. Direct. 16, 23.

  105. Lunghi P., Costanzo A., Mazzera L., Rizzoli V., Massimo Levrero M., Bonati A. (2009) The p53 family protein p73 provides new insights into cancer chemosensitivity and targeting. Clin. Cancer Res. 15, 6495–6502.

  106. Hong B., Prabhu V.V., Zhang S., van den Heuvel A.P.J., Dicker D.T., Kopelovich L, El-Deiry W.S. (2014) Prodigiosin rescues deficient p53 signaling and anti-tumor effects via up-regulating p73 and disrupting its interaction with mutant p53. Cancer Res. 74, 1153–1165. https://doi.org/10.1158/0008-5472.CAN-13-0955

  107. Pietsch E.C., Sykes S.M., McMahon S.B., Murphy M.E. (2008) The p53 family and programmed cell death. Oncogene. 27, 6507–6521.

  108. Toh W.H., Logette E., Corcos L., Sabapathy K. (2008) TAp73b and DNp73b activate the expression of the pro-survival caspase-2S. Nucl. Acids Res. 36, 4498–4509.

  109. Tanaka Y., Kameoka M., Itaya A., Ota K., Yoshihara K. (2004) Regulation of HSF1-responsive gene expression by N-terminal truncated form of p73. Biochem. Biophys. Res. Commun. 317, 865–872. https://doi.org/10.1016/j.bbrc.2004.03.124

  110. Wilhelm M.T., Rufini A., Wetzel M.K., Tsuchihara K., Inoue S., Tomasini R., Itie-Youten A., Wakeham A., Arsenian-Henriksson M., Melino G., Kaplan D.R., Miller F.D., Mak T.W. (2010) Isoform specific p73 knockout mice reveal a novel role for delta Np73 in the DNA damage response pathway. Genes Dev. 24, 549–560.

  111. Виноградская Г.Р. (2013) Белок р73 в канцерогенезе и ответе на противоопухолевую терапию. Вопросы онкологии. 59(2), 42–48.

  112. Engelmann D., Meier C., Alla V., Putzer B.M. (2015) A balancing act: orchestrating amino-truncated and full-length p73 variants as decisive factors in cancer progression. Oncogene. 34, 4287–4299.

  113. Fedorova N.E., Chernoryzh Y.Y., Vinogradskaya G.R., Emelianova S.S., Zavalyshina L.E., Yurlov K.I., Zakirova N.F., Verbenko V.N., Kochetkov S.N., Kushch A.A., Ivanov A.V. (2019) Inhibitor of polyamine catabolism MDL72.527 restores the sensitivity to doxorubicin of monocytic leukemia THP-1 cells infected with human cytomegalovirus. Biochimie. 158, 82–89. https://doi.org/10.1016/j.biochi.2018.12.012

  114. Allart S., Martin H. Detraves C., Terrasson J., Caput D., Davrinche C. (2002) Human cytomegalovirus induces drug resistance and alteration of programmed cell death by accumulation of DN-p73. J. BioI. Chem. 277, 29063–29068.

  115. Емельянова С.С., Чернорыж Я.Ю., Юрлов К.И., Федорова Н.Е., Иванов А.В., Кочетков С.Н., Вербенко В.Н., Кущ А.А., Виноградская Г.Р. (2018) Участие транскрипционных факторов E2F1 и P73 в формировании резистентности к доксорубицину опухолевых клеток THP-1, инфицированных цитомегаловирусом человека. Цитология. 60, 527–530.

  116. Ozaki T., Okoshi R., Ono S., Kubo N., Nakagawara A. (2009) Deregulated expression of E2F1 promotes proteolytic degradation of tumor suppressor p73 and inhibits its transcriptional activity. Biochem. Biophys. Res. Commun. 387, 143–148.

  117. Alla V., Kowtharapu B.S., Engelmann D., Emmrich S., Schmitz U., Steder M., Pulzer B.M. (2012) E2F1 confers anticancer drug resistance by targeting ABC transporter family members and Bcl-2 via the p73/DNp73-miR205 circuitry. Cell Cycle. 11, 3067–3078.

  118. Ferrari E., Gandellini P. (2020) Unveiling the ups and downs of miR-205 in physiology and cancer: transcriptional and post-transcriptional mechanisms. Cell Death Dis. 11, 980. https://doi.org/10.1038/s41419-020-03192-4

  119. Vilgelm A., Wei J.X., Piazuelo M.B., Washington M.K, Prassolov V., El-Rifai W., Zaika A. (2008) ΔNp73α regulates MDR1 expression by inhibiting p53 function. Oncogene. 27, 2170–2176. https://doi.org/10.1038/sj.onc.1210862

  120. Terrasson J., Allart S., Martin H., Lulé J., Haddada H., Caput D., Davrinche C. (2005) P73-dependent apoptosis through death receptor: impairment by human cytomegalovirus infection. Cancer Res. 65, 2787–2794.

  121. Logotheti S., Richter C., Murr N., Spitschak A., Marquardt S., Pützer B.M. (2021) Mechanisms of functional pleiotropy of p73 in cancer and beyond. Front. Cell. Dev. Biol. 9, 737735. https://doi.org/10.3389/fcell.2021.737735.34650986

  122. Liu T., Roh S.E., Woo J.A., Ryu H., Kang D.E. (2013) Cooperative role of RanBP9 and P73 in mitochondria-mediated apoptosis. Cell Death Dis. 4, e476.

  123. Maisse C., Munarriz E., Barcaroli D., Melino G., De Laurenzi V. (2004) DNA damage induces the rapid and selective degradation of the DNp73 isoform, allowing apoptosis to occur. Cell Death Differ. 11, 685–687.

  124. Daskalos A., Logotheti S., Markopoulou S., Xinarianos G., Gosney J.R., Kastania A.N., Zoumpourlis V., Field J.K., Liloglou T. (2011) Global DNA hypomethylation-induced DeltaNp73 transcriptional activation in non-small cell lung cancer. Cancer Lett. 300, 79–86.

  125. Casciano I., Banelli B., Croce M., Allemanni G., Ferrini S., Tonini G.P., Ponzoni M., Romani M. (2002) Role of methylation in the control of DeltaNp73 expression in neuroblastoma. Cell Death Differ. 9, 343–345.

  126. Lai J., Nie W., Zhang W., Wang Y., Xie R., Wang Y., Gu J., Xu J., Song W., Yang F., Huang G., Cao P., Guan X. (2014) Transcriptional regulation of the p73 gene by Nrf-2 and promoter CpG methylation in human breast cancer. Oncotarget. 5, 6909–6922.

  127. Sayan B.S., Yang A.L., Conforti F., Tucci P., Piro M.C., Browne G.J., (2010) Differential control of TAp73 and DNp73 protein stability by the ring finger ubiquitin ligase PIR2. Proc. Natl. Acad. Sci. USA. 107, 12877–12882.

  128. Taebunpakul P., Sayan B.S., Flinterman M., Klanrit P., Gäken J., Odell E.W., Melino G., Tavassoli M. (2012) Apoptin induces apoptosis by changing the equilibrium between the stability of TAp73 and ΔNp73 isoforms through ubiquitin ligase PIR2. Apoptosis. 17, 762–776. https://doi.org/10.1007/s10495-012-0720-7

  129. Chaudhary N., Maddika S. (2014) WWP2-WWP1 ubiquitin ligase complex coordinated by PPM1G maintains the balance between cellular p73 and DNp73 levels. Mol. Cell. Biol. 34, 3754–3764.

  130. Bunjobpol W., Dulloo I., Igarashi K., Concin N., Matsuo K., Sabapathy K. (2014) Suppression of ace-tylpolyamine oxidase by selected AP-1 members regulates DNp73 abundance: mechanistic insights for overcoming DNp73-mediated resistance to chemotherapeutic drugs. Cell Death Differ. 21, 1240–1249.

  131. Cao W., Li J., Yang K., Cao D. (2021) An overview of autophagy: mechanism, regulation and research progress. Bull. Cancer. 108, 304–322. https://doi.org/10.1016/j.bulcan.2020.11.004

  132. Yu L., Wan F., Dutta S., Welsh S., Liu Z., Freundt E., Baehrecke E.H., Lenardo M. (2006) Autophagic programmed cell death by selective catalase degradation. Proc. Natl. Acad. Sci. USA. 103, 4952–4957. https://doi.org/10.1073/pnas.0511288103

  133. Cui J., Zhao S., Li Y., Zhang D., Wang B., Xie J., Wang J. (2021) Regulated cell death: discovery, features and implications for neurodegenerative diseases. Cell Commun. Signal. 19, 120. https://doi.org/10.1186/s12964-021-00799-8

  134. Шляпина В.Л., Юртаева С.В., Рубцова М.П., Донцова О.А. (2021) На распутье: механизмы апоптоза и аутофагии в жизни и смерти клетки. Acta Naturae. 13, № 2(49). 106‒115.

  135. Babaei G., Aziz S.G., Jaghi N.Z.Z. (2021) EMT, cancer stem cells and autophagy; the three main axes of metastasis. Biomed. Pharmacother. 133, 110909. https://doi.org/10.1016/j.biopha.2020.110909

  136. Urbańska K., Orzechowski A. (2021) The secrets of alternative autophagy. Cells. 10, 3241. https://doi.org/10.3390/cells10113241

  137. Gómez-Sánchez R., Rose J., Guimarães R., Mari M., Papinski D., Rieter E., Geerts W.J., Hardenberg R., Kraft C., Ungermann C., Reggiori F. (2018) Atg9 establishes Atg2-dependent contact sites between the endoplasmic reticulum and phagophores. J. Cell. Biol. 217, 2743–2763. https://doi.org/10.1083/jcb.201710116

  138. Li X., He S., Ma B. (2020) Autophagy and autophagy-related proteins in cancer. Mol. Cancer. 19(1), 12. https://doi.org/10.1186/s12943-020-1138-4

  139. Bujak A.L., Crane J.D., Lally J.S., Ford R.J., Kang S.J., Rebalka I.A., Green A.E., Kemp B.E., Hawke T.J., Schertzer J.D., Gregory R Steinberg G.R. (2015) AMPK activation of muscle autophagy prevents fasting-induced hypoglycemia and myopathy during aging. Cell. Metab. 21, 883–890. https://doi.org/10.1016/j.cmet.2015.05.016

  140. Hill S.M., Wrobel L., Rubinsztein D.C. (2019) Post-translational modifications of Beclin 1 provide multiple strategies for autophagy regulation. Cell Death Differ. 26, 617–629. https://doi.org/10.1038/s41418-018-0254-9

  141. Klionsky D.J., Abdelmohsen K., Abe A., et al. The consortium (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 12, 1–222. https://doi.org/10.1080/15548627.2015.1100356.26799652

  142. Pradel B., Robert-Hebmann V., Espert L. (2020) Regulation of innate immune responses by autophagy: a goldmine for viruses. Front. Immunol. 11, 578038. https://doi.org/10.3389/fimmu.2020.578038

  143. Sharma V., Verma S., Seranova E., Sarkar S., Kumar D. (2018) Selective autophagy and xenophagy in infection and disease. Front. Cell. Dev. Biol. 6, 147. https://doi.org/10.3389/fcell.2018.00147

  144. Choi Y., Bowman J.W., Jung J.U. (2018) Autophagy during viral infection – a double-edged sword. Nat. Rev. Microbiol. 16, 341–354. https://doi.org/10.1038/s41579-018-0003-6

  145. Mijaljica D., Klionsky D.J. (2020) Autophagy/virophagy: a “disposal strategy” to combat COVID-19. Autophagy. 16, 2271–2272. https://doi.org/10.1080/15548627.2020.1782022

  146. Leonardi L., Sibéril S., Alifano M., Cremer I., Joubert P.E. (2021) Autophagy modulation by viral infections influences tumor development. Front. Oncol. 11, 743780. https://doi.org/10.3389/fonc.2021.743780

  147. Liang W., Liu H., He J., Ai L., Meng Q., Zhang W., Yu C., Wang H., Liu H. (2021) Studies progression on the function of autophagy in viral infection. Front. Cell. Dev. Biol. 9, 772965. https://doi.org/0.3389/fcell.2021.772965

  148. Mouna L., Hernandez E., Bonte D., Brost R., Amazit L., Delgui L.R., Brune W., Geballe A.P., Beau I., Esclatinea A. (2016) Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins. Autophagy. 12, 327–342.

  149. Belzile J.P., Sabalza M., Craig M., Clark A.E., Morello C.S., Spector D.H. (2016) Trehalose, an mTOR-independent inducer of autophagy, inhibits human cytomegalovirus infection in multiple cell types. J. Virol. 90, 1259–1277.

  150. Zhang X., Zhang L., Bi Y., Xi T., Zhang Z., Huang Y., Lu Y.Y., Liu X., Shu S., Fang F. (2021) Inhibition of autophagy by 3-methyladenine restricts murine cytomegalovirus replication. J. Med. Virol. 93, 5001–5016. https://doi.org/10.1002/jmv.26787

  151. Zimmermann C., Krämer N., Krauter S., Strand D., Sehn E., Wolfrum U., Freiwald A., Butter F., Plachter B. (2021) Autophagy interferes with human cytomegalovirus genome replication, morphogenesis, and progeny release. Autophagy. 17, 779–795. https://doi.org/10.1080/15548627.2020.1732686

  152. Zhang X., Xi T., Zhang L., Bi Y., Huang Y., Lu Y., Liu X., Fang F. (2021) The role of autophagy in human cytomegalovirus IE2 expression. J. Med. Virol. 93, 3795–3803. https://doi.org/10.1002/jmv.26357

  153. Liu Y., Pan J., Liu L., Li W., Tao R., Chen Y., Li H., Shang S. (2017) The influence of HCMV infection on autophagy in THP-1 cells. Medicine (Baltimore). 96, e8298. https://doi.org/10.1097/MD.0000000000008298

  154. Chaumorcel M., Souquère S., Pierron G., Codogno P., Esclatine A. (2008) Human cytomegalovirus controls a new autophagy-dependent cellular antiviral defense mechanism. Autophagy. 4(1), 46–53. https://doi.org/10.4161/auto.5184

  155. Tovilovic G., Ristic B., Siljic M., Nikolic V., Kravic-Stevovic T., Dulovic M., Milenkovic M., Knezevic A., Bosnjak M., Bumbasirevic V., Stanojevic M., Trajko-vic V. (2013) mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells. Microbes Infect. 15(8–9), 615–624. https://doi.org/10.1016/j.micinf.2013.04.012

  156. Usman R.M., Razzaq F., Akbar A., Farooqui A.A., Iftikhar A., Latif A., Hassan H., Zhao J., Carew J.S., Nawrocki S.T., Anwer F. (2021) Role and mechanism of autophagy-regulating factors in tumorigenesis and drug resistance. Asia Pac. J. Clin. Oncol. 17, 193–208. https://doi.org/10.1111/ajco.13449

  157. Chiou J.T., Huang C.H., Lee Y.C., Wang L.J., Shi Y.J., Chen Y.J., Chang L.-S. (2020) Compound C induces autophagy and apoptosis in parental and hydroquinone-selected malignant leukemia cells through the ROS/p38 MAPK/AMPK/TET2/FOXP3 axis. Cell Biol Toxicol. 36, 315–331.

  158. Linder B., Kögel D. (2019) Autophagy in cancer cell death. Biology. 8(4), 82. https://doi.org/10.3390/biology8040082

  159. Tao Z., Li T., Ma H., Yang Y., Zhang C., Hai L., Liu P., Yuan F., Li J., Yi L., Tong L., Wang Y., Xie Y., Ming H., Yu S., Yang X. (2018) Autophagy suppresses self-renewal ability and tumorigenicity of glioma-initiating cells and promotes Notch1 degradation. Cell Death Dis. 9, 1063. https://doi.org/10.1038/s41419-018-0957-3

  160. Barthet V.J.A., Brucoli M., Ladds M., Nössing C., Kiourtis C., Baudot A.D., O’Prey J., Zunino B., Mül-ler M., May S., Nixon C., Long J.S., Bird T.G., Ryan K.M. (2021) Autophagy suppresses the formation of hepatocyte-derived cancer-initiating ductular progenitor cells in the liver. Sci. Adv. 7, eabf9141. https://doi.org/10.1126/sciadv.abf9141

  161. Zhu H., Wang D., Zhang L., Xie X., Wu Y., Liu Y., Shao G., Su Z. (2014) Upregulation of autophagy by hypoxia-inducible factor-1α promotes EMT and metastatic ability of CD133+ pancreatic cancer stem-like cells during intermittent hypoxia. Oncol. Rep. 32, 935–942. https://doi.org/10.3892/or.2014.3298

  162. Zhu Y., Huang S., Chen S., Chen J., Wang Z., Wang Y., Zheng H. (2021) SOX2 promotes chemoresistance, cancer stem cells properties, and epithelial-mesenchymal transition by β-catenin and Beclin1/autophagy signaling in colorectal cancer. Cell Death Dis. 12, 449. https://doi.org/10.1038/s41419-021-03733-5

  163. Zhou Q., Cui F., Lei C., Ma S., Huang J., Wang X., Qian H., Zhang D., Yang Y. (2021) ATG7-mediated autophagy involves in miR-138-5p regulated self-renewal and invasion of lung cancer stem-like cells derived from A549 cells. Anti-Cancer Drugs. 32, 376–385. https://doi.org/10.1097/CAD.0000000000000979

  164. Wang X., Lee J., Xie C. (2022) Autophagy regulation on cancer stem cell maintenance, metastasis, and therapy resistance. Cancers (Basel). 14, 381. https://doi.org/10.3390/cancers14020381

  165. Bao L., Jaramillo M.C., Zhang Z., Zheng Y., Yao M., Zhang D.D., Yi X. (2015) Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells. Mol. Med. Rep. 11, 91–98. https://doi.org/10.3892/mmr.2014.2671

  166. Cheng C.Y., Liu J.C., Wang J.J., Li Y.H., Pan J., Zhang Y.R. (2017) Autophagy inhibition increased the anti-tumor effect of cisplatin on drug-resistant esophageal cancer cells. J. Biol. Regul. Homeost. Agents. 31, 645–652.

  167. Yang J., Pi C., Wang G. (2018) Inhibition of PI3K/ Akt/mTOR pathway by apigenin induces apoptosis and autophagy in hepatocellular carcinoma cells. Biomed. Pharmacother. 103, 699–707. https://doi.org/10.1016/j.biopha.2018.04.072

  168. Liu K., Ren T., Huang Y., Sun K., Bao X., Wang S., Zheng B., Guo W. (2017) Apatinib promotes autophagy and apoptosis through VEGFR2/STAT3/BCL-2 signaling in osteosarcoma. Cell Death Dis. 8, e3015. https://doi.org/10.1038/cddis.2017.422

  169. Antonioli M., Pagni B., Vescovo T., Ellis R., Cosway B., Rollo F., Bordonia V., Agratia C., Labus M., Covelloe R., Benevoloe M., Ippolitoa G., Robinson M., Piacentini M., Lovatc P., Fimia G.M. (2021) HPV sensitizes OPSCC cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1. Autophagy. 17, 2842–2855. https://doi.org/10.1080/15548627.2020.1847444

  170. Чернорыж Ю.Ю., Федорова Н.Е., Юрлов К.И., Симонов Р.А., Корнев А.В., Карпов Д.С., Закирова Н.Ф., Иванов А.В., Кущ А.А., Гинцбург А.Л. (2019) Резистентность клеток лейкемии ТНР-1, инфицированных цитомегаловирусом, к противоопухолевому антибиотику доксорубицину и восстановление чувствительности ингибиторами молекулярного пути PI3K/AKT/mTOR. Докл. Акад. Наук: биохимия, биофизика, молекуляр. биология. 489(4), 433‒437.

  171. Chang P.H., Graham J., Hao J., Ni J., Bucci N.J., Cozzi P.J., Kearsley J.H., Li Y. (2013) Acquisition of epithelial-mesenchymal cancer stem cell phenotypes is associated with activation of the PI3K/Akt/mTOR pathway in prostate cancer radioresistance. Cell Death Dis. 4, e875. https://doi.org/10.1038/cddis.2013.407

  172. Galluzzi L., Pedro J.M.B.-S., Levine B., Green D.R., Kroemer G. (2017) Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat. Rev. Drug Discov. 16, 487–511. https://doi.org/10.1038/nrd.2017.22

  173. Prerna K., Dubey V.K. (2021) Repurposing of FDA-approved drugs as autophagy inhibitors in tumor cells. J. Biomol. Struct. Dyn. 20, 1–12. https://doi.org/10.1080/07391102.2021.1873862

  174. Xie Q., Liu Y., Li X. (2020) The interaction mechanism between autophagy and apoptosis in colon cancer. Transl. Oncol. 13, 100871. https://doi.org/10.1016/j.tranon.2020.100871

Дополнительные материалы отсутствуют.