Autophagy in the physiological endometrium and cancer

References

• Farré J-C, Subramani S. Mechanistic insights into selective autophagy pathways: lessons from yeast. Nat Rev Mol Cell Biol. 2016;17:537–552.
   PubMed Web of Science ®Google Scholar
• Ryter SW, Cloonan SM, Choi AMK. Autophagy: a critical regulator of cellular metabolism and homeostasis. Mol Cells. 2013;36:7–16.
   PubMed Web of Science ®Google Scholar
• Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12:1–222.
   PubMed Web of Science ®Google Scholar
• Yu L, Chen Y, Tooze SA. Autophagy pathway: cellular and molecular mechanisms. Autophagy. 2018;14:207–215.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Baehrecke EH, Ballabio A, et al. Molecular definitions of autophagy and related processes. Embo J. 2017;36:1811–1836.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Bravo-San Pedro JM, Levine B, et al. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov. 2017;16:487–511.
   PubMed Web of Science ®Google Scholar
• Cuervo AM, Wong E. Chaperone-mediated autophagy: roles in disease and aging. Cell Res. 2014;24:92–104.
   PubMed Web of Science ®Google Scholar
• Kaushik S, Cuervo AM. Chaperone-mediated autophagy: a unique way to enter the lysosome world. Trends Cell Biol. 2012;22:407–417.
   PubMed Web of Science ®Google Scholar
• Mijaljica D, Prescott M, Devenish RJ. Microautophagy in mammalian cells: revisiting a 40-year-old conundrum. Autophagy. 2011;7:673–682.
   PubMed Web of Science ®Google Scholar
• Mizushima N, Yoshimori T, Ohsumi Y. The role of atg proteins in autophagosome formation. Annu Rev Cell Dev Biol. 2011;27:107–132.
   PubMed Web of Science ®Google Scholar
• Noda NN, Inagaki F. Mechanisms of autophagy. Annu Rev Biophys. 2015;44:101–122.
   PubMed Web of Science ®Google Scholar
• Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004;6:463–477.
   PubMed Web of Science ®Google Scholar
• Lamb CA, Yoshimori T, Tooze SA. The autophagosome: origins unknown, biogenesis complex. Nat Rev Mol Cell Biol. 2013;14:759–774.
   PubMed Web of Science ®Google Scholar
• Green DR, Galluzzi L, Kroemer G. Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science. 2011;333:1109–1112.
   PubMed Web of Science ®Google Scholar
• Mizushima N, Levine B. Autophagy in mammalian development and differentiation. Nat Cell Biol. 2010;12:823–830.
   PubMed Web of Science ®Google Scholar
• Beier HM, Beier-Hellwig K. Molecular and cellular aspects of endometrial receptivity. Hum Reprod Update. 1998;4:448–458.
   PubMed Web of Science ®Google Scholar
• Ruiz-Alonso M, Blesa D, Simón C. The genomics of the human endometrium. Biochim Biophys Acta - Mol Basis Dis. 2012;1822:1931–1942.
   Web of Science ®Google Scholar
• Talbi S, Hamilton AE, Vo KC, et al. Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women. Endocrinology. 2006;147:1097–1121.
   PubMed Web of Science ®Google Scholar
• Harada T, Kaponis A, Iwabe T, et al. Apoptosis in human endometrium and endometriosis. Hum Reprod Update. 2004;10:29–38.
   PubMed Web of Science ®Google Scholar
• Bulun S, Adashi E. The Physiology and Pathology of the Female Reproductive Axis. In: Kronenberg HM, Melmed S, Polonsky KS, et al., editors. Williams textbook of endocrinology. Philadelphia, PA:Elsevier Health Sciences; 2007. p. 587–663.
   Google Scholar
• Choi J, Jo M, Lee E, et al. The role of autophagy in human endometrium. Biol Reprod. 2012;86:70.
   PubMed Web of Science ®Google Scholar
• Cakmak H, Taylor HS. Implantation failure: molecular mechanisms and clinical treatment. Hum Reprod Update. 2011;17:242–253.
   PubMed Web of Science ®Google Scholar
• Su R-W, Fazleabas AT. Implantation and establishment of pregnancy in human and nonhuman primates. Adv Anat Embryol Cell Biol. 2015;216:189–213.
   PubMed Web of Science ®Google Scholar
• Kim S-M, Kim J-S. A review of mechanisms of implantation. Dev Reprod. 2017;21:351–359.
   PubMedGoogle Scholar
• Cornillie FJ, Lauweryns JM, Brosens IA. Normal human Endometrium. Gynecol Obstet Invest. 1985;20:113–129.
   PubMed Web of Science ®Google Scholar
• Lawn AM, Wilson EW, Finn CA. The ultrastructure of human decidual and predecidual cells. J Reprod Fertil. 1971;26:85–90.
   PubMedGoogle Scholar
• Avagliano L, Terraneo L, Virgili E, et al. Autophagy in normal and abnormal early human pregnancies. Reprod Sci. 2015;22:838–844.
   PubMed Web of Science ®Google Scholar
• Mestre Citrinovitz AC, Strowitzki T, Germeyer A. Decreased autophagy impairs decidualization of human endometrial stromal cells: a role for ATG proteins in endometrial physiology. Int J Mol Sci. 2019;20:3066.
   Web of Science ®Google Scholar
• Rhee JS, Saben JL, Mayer AL, et al. Diet-induced obesity impairs endometrial stromal cell decidualization: a potential role for impaired autophagy. Hum Reprod. 2016;31:1315–1326.
   PubMed Web of Science ®Google Scholar
• Talmor A, Dunphy B. Female obesity and infertility. Best Pract Res Clin Obstet Gynaecol. 2015;29:498–506.
   PubMed Web of Science ®Google Scholar
• Boots CE, Bernardi LA, Stephenson MD. Frequency of euploid miscarriage is increased in obese women with recurrent early pregnancy loss. Fertil Steril. 2014;102:455–459.
   PubMed Web of Science ®Google Scholar
• Luzzo KM, Wang Q, Purcell SH, et al. High fat diet induced developmental defects in the mouse: oocyte meiotic aneuploidy and fetal growth retardation/brain defects. PLoS One. 2012;7:e49217.
   PubMed Web of Science ®Google Scholar
• Nakashima A, Aoki A, Kusabiraki T, et al. Role of autophagy in oocytogenesis, embryogenesis, implantation, and pathophysiology of pre-eclampsia. J Obstet Gynaecol Res. 2017;43:633–643.
   PubMed Web of Science ®Google Scholar
• Zhou S, Zhao L, Yi T, et al. Menopause-induced uterine epithelium atrophy results from arachidonic acid/prostaglandin E2 axis inhibition-mediated autophagic cell death. Sci Rep. 2016;6:31408.
   PubMed Web of Science ®Google Scholar
• Zhang D, Li J, Xu G, et al. Follicle-stimulating hormone promotes age-related endometrial atrophy through cross-talk with transforming growth factor beta signal transduction pathway. Aging Cell. 2015;14:284–287.
   PubMed Web of Science ®Google Scholar
• Santoro N, Randolph JF. Reproductive hormones and the menopause transition. Obstet Gynecol Clin North Am. 2011;38:455–466.
   PubMed Web of Science ®Google Scholar
• Sanderson PA, Critchley HOD, Williams ARW, et al. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Hum Reprod Update. 2017;23:232–254.
   PubMed Web of Science ®Google Scholar
• Baak JPA, Mutter GL. EIN and WHO94. J Clin Pathol. 2005;58:1–6.
   PubMed Web of Science ®Google Scholar
• Mutter GL. Endometrial intraepithelial Neoplasia (EIN): will it bring order to Chaos? Gynecol Oncol. 2000;76:287–290.
   PubMed Web of Science ®Google Scholar
• Jarboe EA, Mutter GL. Endometrial intraepithelial neoplasia. Semin Diagn Pathol. 2010;27:215–225.
   PubMed Web of Science ®Google Scholar
• Feng L, Li J, Yang L, et al. Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia. Theranostics. 2017;7:1890–1900.
   PubMed Web of Science ®Google Scholar
• Strissel PL, Ellmann S, Loprich E, et al. Early aberrant insulin-like growth factor signaling in the progression to endometrial carcinoma is augmented by tamoxifen. Int J Cancer. 2008;123:2871–2879.
   PubMed Web of Science ®Google Scholar
• Lin BC, Suzawa M, Blind RD, et al. Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation. Cancer Res. 2009;69:5415–5423.
   PubMed Web of Science ®Google Scholar
• Sivridis E, Giatromanolaki A, Liberis V, et al. Autophagy in endometrial carcinomas and prognostic relevance of “stone-like” structures (SLS): what is destined for the atypical endometrial hyperplasia? Autophagy. 2011;7:74–82.
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30.
   PubMed Web of Science ®Google Scholar
• Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.
   PubMed Web of Science ®Google Scholar
• Sorosky JI. Endometrial cancer. Obstet Gynecol. 2012;120(2, Part 1):383–397.
   PubMed Web of Science ®Google Scholar
• Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15(1):10–17.
   PubMed Web of Science ®Google Scholar
• Matias-Guiu X, Prat J. Molecular pathology of endometrial carcinoma. Histopathology. 2013;62(1):111–123.
   PubMed Web of Science ®Google Scholar
• Llobet D, Pallares J, Yeramian A, et al. Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints. J Clin Pathol. 2009;62(9):777–785.
   PubMed Web of Science ®Google Scholar
• Matias-Guiu X, Davidson B. Prognostic biomarkers in endometrial and ovarian carcinoma. Virchows Arch. 2014;464(3):315–331.
   PubMed Web of Science ®Google Scholar
• Levine DA, Getz G, Gabriel S, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73.
   PubMed Web of Science ®Google Scholar
• Lebovitz CB, Robertson AG, Goya R, et al. Cross-cancer profiling of molecular alterations within the human autophagy interaction network. Autophagy. 2015;11(9):1668–1687.
   PubMed Web of Science ®Google Scholar
• Budina-Kolomets A, Hontz RD, Pimkina J, et al. A conserved domain in exon 2 coding for the human and murine ARF tumor suppressor protein is required for autophagy induction. Autophagy. 2013;9(10):1553–1565.
   PubMed Web of Science ®Google Scholar
• Yemelyanova A, Ji H, Shih I-M, et al. Utility of p16 expression for distinction of uterine serous carcinomas from endometrial endometrioid and endocervical adenocarcinomas. Am J Surg Pathol. 2009;33(10):1504–1514.
   PubMed Web of Science ®Google Scholar
• Giatromanolaki A, Koukourakis MI, Koutsopoulos A, et al. High Beclin 1 expression defines a poor prognosis in endometrial adenocarcinomas. Gynecol Oncol. 2011;123(1):147–151.
   PubMed Web of Science ®Google Scholar
• Zhao J-H, Wan X-Y, Xie X, et al. Expression and clinical significance of Beclin1 and PTEN in endometrial carcinoma. Ai Zheng Internet. 2006;25:753–757.
   PubMedGoogle Scholar
• Orfanelli T, Jeong JM, Doulaveris G, et al. Involvement of autophagy in cervical, endometrial and ovarian cancer. Int J Cancer. 2014;135(3):519–528.
   PubMed Web of Science ®Google Scholar
• Deng L. Identification of a novel estrogen-regulated gene, EIG121, induced by hormone replacement therapy and differentially expressed in type I and Type II endometrial cancer. Clin Cancer Res. 2005;11(23):8258–8264.
   PubMed Web of Science ®Google Scholar
• Deng L, Feng J, Broaddus RR. The novel estrogen-induced gene EIG121 regulates autophagy and promotes cell survival under stress. Cell Death Dis. 2010;1(4):e32–e32.
   PubMedGoogle Scholar
• Nout RA, Smit VTHBM, Putter H, et al. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet. 2010;375(9717):816–823.
   PubMed Web of Science ®Google Scholar
• Blake P, Swart AM, Orton J, et al.; ASTEC/EN.5 Study Group. Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis. Lancet. 2009;373:137–146.
   PubMed Web of Science ®Google Scholar
• Tangjitgamol S, See HT, Kavanagh J. Adjuvant chemotherapy for endometrial cancer. Int J Gynecol Cancer. 2011;21(5):885–895.
   PubMed Web of Science ®Google Scholar
• Fleming GF. Systemic chemotherapy for uterine carcinoma: metastatic and adjuvant. J Clin Oncol. 2007;25(20):2983–2990.
   PubMed Web of Science ®Google Scholar
• Eritja N, Yeramian A, Chen B-J, et al. Endometrial carcinoma: specific targeted pathways. Adv Exp Med Biol. 2017;943:149–207.
   PubMed Web of Science ®Google Scholar
• Santaballa A, Matías-Guiu X, Redondo A, et al. SEOM clinical guidelines for endometrial cancer (2017). Clin Transl Oncol. 2018;20(1):29–37.
   PubMed Web of Science ®Google Scholar
• Morselli E, Galluzzi L, Kepp O, et al. Anti- and pro-tumor functions of autophagy. Biochim Biophys Acta Mol Cell Res. 2009;1793(9):1524–1532.
   Web of Science ®Google Scholar
• Mohammad RM, Muqbil I, Lowe L, et al. Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol. 2015;35:S78–103.
   PubMed Web of Science ®Google Scholar
• Notte A, Leclere L, Michiels C. Autophagy as a mediator of chemotherapy-induced cell death in cancer. Biochem Pharmacol. 2011;82(5):427–434.
   PubMed Web of Science ®Google Scholar
• Shintani T. Autophagy in health and disease: a double-edged sword. Science. 2004;306(5698):990–995.
   PubMed Web of Science ®Google Scholar
• Fukuda T, Oda K, Wada-Hiraike O, et al. The anti-malarial chloroquine suppresses proliferation and overcomes cisplatin resistance of endometrial cancer cells via autophagy inhibition. Gynecol Oncol. 2015;137(3):538–545.
   PubMed Web of Science ®Google Scholar
• Sun M-Y, Zhu J-Y, Zhang C-Y, et al. Autophagy regulated by lncRNA HOTAIR contributes to the cisplatin-induced resistance in endometrial cancer cells. Biotechnol Lett. 2017;39(10):1477–1484.
   PubMed Web of Science ®Google Scholar
• Lin Q, Wang Y, Chen D, et al. Cisplatin regulates cell autophagy in endometrial cancer cells via the PI3K/AKT/mTOR signalling pathway. Oncol Lett. 2017;13(5):3567–3571.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Anderson KC. Bortezomib: a novel therapy approved for multiple myeloma. Clin Adv Hematol Oncol. 2003;1(10):596–600.
   PubMedGoogle Scholar
• Dolcet X, Llobet D, Encinas M, et al. Proteasome inhibitors induce death but activate NF-κB on endometrial carcinoma cell lines and primary culture explants. J Biol Chem. 2006;281(31):22118–22130.
   PubMed Web of Science ®Google Scholar
• Periyasamy-Thandavan S, Jackson WH, Samaddar JS, et al. Bortezomib blocks the catabolic process of autophagy via a cathepsin-dependent mechanism, affects endoplasmic reticulum stress, and induces caspase-dependent cell death in antiestrogen–sensitive and resistant ER+ breast cancer cells. Autophagy. 2010;6(1):19–35.
   PubMed Web of Science ®Google Scholar
• Hong YS, Hong S-W, Kim S-M, et al. Bortezomib induces G2-M arrest in human colon cancer cells through ROS-inducible phosphorylation of ATM-CHK1. Int J Oncol. 2012;41(1):76–82. .
   PubMed Web of Science ®Google Scholar
• Befani CD, Vlachostergios PJ, Hatzidaki E, et al. Bortezomib represses HIF-1α protein expression and nuclear accumulation by inhibiting both PI3K/Akt/TOR and MAPK pathways in prostate cancer cells. J Mol Med. 2012;90(1):45–54.
   PubMed Web of Science ®Google Scholar
• Chen D, Frezza M, Schmitt S, et al. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets. 2011;11(3):239–253.
   PubMed Web of Science ®Google Scholar
• Kao C, Chao A, Tsai C-L, et al. Bortezomib enhances cancer cell death by blocking the autophagic flux through stimulating ERK phosphorylation. Cell Death Dis. 2014;5(11):e1510–e1510.
   PubMedGoogle Scholar
• Eckschlager T, Plch J, Stiborova M, et al. Histone deacetylase inhibitors as anticancer drugs. Int J Mol Sci. 2017;18(7):1414.
   PubMed Web of Science ®Google Scholar
• De Umasankar U, Son J, Sachan R, et al. A new synthetic histone deacetylase inhibitor, MHY2256, induces apoptosis and autophagy cell death in endometrial cancer cells via p53 acetylation. Int J Mol Sci. 2018;19(9):2743.
   Web of Science ®Google Scholar
• Zhou W-J, Chang -K-K, Wu K, et al. Rapamycin synergizes with cisplatin in antiendometrial cancer activation by improving IL-27–stimulated cytotoxicity of NK cells. Neoplasia. 2018;20(1):69–79.
   PubMed Web of Science ®Google Scholar
• Zingoni A, Fionda C, Borrelli C, et al. Natural killer cell response to chemotherapy-stressed cancer cells: role in tumor immunosurveillance. Front Immunol. 2017;8:1194.
   PubMed Web of Science ®Google Scholar
• Vandenput I, Vergote I, Leunen K, et al. Leuven dose-dense paclitaxel/carboplatin regimen in patients with primary advanced or recurrent endometrial carcinoma. Int J Gynecol Cancer. 2009;19(6):1147–1151.
   PubMed Web of Science ®Google Scholar
• Sorbe B, Andersson H, Boman K, et al. Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxellong-term follow-up. Int J Gynecol Cancer. 2008;18(4):803–808.
   PubMed Web of Science ®Google Scholar
• Felip I, Moiola CP, Megino-Luque C, et al. Therapeutic potential of the new TRIB3-mediated cell autophagy anticancer drug ABTL0812 in endometrial cancer. Gynecol Oncol. 2019;153(2):425–435. .
   PubMed Web of Science ®Google Scholar
• Liu S, Li X. Autophagy inhibition enhances sensitivity of endometrial carcinoma cells to paclitaxel. Int J Oncol. 2015;46(6):2399–2408.
   PubMed Web of Science ®Google Scholar
• Ran X, Yang J, Liu C, et al. MiR-218 inhibits HMGB1-mediated autophagy in endometrial carcinoma cells during chemotherapy. Int J Clin Exp Pathol. 2015;8(6):6617–6626.
   PubMed Web of Science ®Google Scholar
• Wang H, Li D, Li X, et al. Mammalian target of rapamycin inhibitor RAD001 sensitizes endometrial cancer cells to paclitaxel-induced apoptosis via the induction of autophagy. Oncol Lett. 2016;12(6):5029–5035.
   PubMed Web of Science ®Google Scholar
• Ran X, Zhou P, Zhang K. Autophagy plays an important role in stemness mediation and the novel dual function of EIG121 in both autophagy and stemness regulation of endometrial carcinoma JEC cells. Int J Oncol. 2017;51(2):644–656.
   PubMed Web of Science ®Google Scholar
• Yoshida GJ. Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res. 2015;34(1):111.
   PubMedGoogle Scholar
• Kasznicki J, Sliwinska A, Drzewoski J. Metformin in cancer prevention and therapy. Ann Transl Med. 2014;2:57.
   PubMedGoogle Scholar
• Quinn BJ, Kitagawa H, Memmott RM, et al. Repositioning metformin for cancer prevention and treatment. Trends Endocrinol Metab. 2013;24(9):469–480.
   PubMed Web of Science ®Google Scholar
• Meng S, Cao J, He Q, et al. Metformin activates AMP-activated protein kinase by promoting formation of the αβγ heterotrimeric complex. J Biol Chem. 2015;290(6):3793–3802.
   PubMed Web of Science ®Google Scholar
• Ben Sahra I, Regazzetti C, Robert G, et al. Metformin, Independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res. 2011;71(13):4366–4372.
   PubMed Web of Science ®Google Scholar
• Takahashi A, Kimura F, Yamanaka A, et al. Metformin impairs growth of endometrial cancer cells via cell cycle arrest and concomitant autophagy and apoptosis. Cancer Cell Int. 2014;14(1):53.
   PubMedGoogle Scholar
• Nadkarni P, Chepurny OG, Holz GG. Regulation of glucose homeostasis by GLP-1. Prog Mol Biol Transl Sci. 2014;121:23–65.
   PubMed Web of Science ®Google Scholar
• Kanda R, Hiraike H, Wada-Hiraike O, et al. Expression of the glucagon-like peptide-1 receptor and its role in regulating autophagy in endometrial cancer. BMC Cancer. 2018;18(1):657.
   PubMedGoogle Scholar
• Zhou W-J, Zhang J, Yang H-L, et al. Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism. Cell Commun Signal. 2019;17(1):99.
   PubMed Web of Science ®Google Scholar
• Gu C-J, Cheng J, Zhang B, et al. Protopanaxadiol and metformin synergistically inhibit estrogen-mediated proliferation and anti-autophagy effects in endometrial cancer cells. Am J Transl Res. 2017;9(9):4071–4082.
   PubMed Web of Science ®Google Scholar
• Yu Y, Zhou Q, Hang Y, et al. Antiestrogenic effect of 20S-protopanaxadiol and its synergy with tamoxifen on breast cancer cells. Cancer. 2007;109(11):2374–2382.
   PubMed Web of Science ®Google Scholar
• Kim J, Chapman-Davis E. Role of progesterone in endometrial cancer. Seminars in Reproductive Medicine. 2010;28(1):081–90.
   PubMed Web of Science ®Google Scholar
• Dizon DS. Treatment options for advanced endometrial carcinoma. Gynecol Oncol. 2010;117(2):373–381.
   PubMed Web of Science ®Google Scholar
• Zhuo Z, Wang A, Yu H. Metformin targeting autophagy overcomes progesterone resistance in endometrial carcinoma. Arch Gynecol Obstet. 2016;294(5):1055–1061.
   PubMed Web of Science ®Google Scholar
• Liu H, Zhang L, Zhang X, et al. PI3K/AKT/mTOR pathway promotes progestin resistance in endometrial cancer cells by inhibition of autophagy. Onco Targets Ther. 2017;10:2865–2871.
   PubMed Web of Science ®Google Scholar
• Zhao S, Li G, Yang L, et al. Response-specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long-term exposure to medroxyprogesterone acetate. Oncol Lett. 2013;5(1):139–144.
   PubMed Web of Science ®Google Scholar
• Gschwind A, Fischer OM, Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer. 2004;4(5):361–370.
   PubMed Web of Science ®Google Scholar
• Knight ZA, Lin H, Shokat KM. Targeting the cancer kinome through polypharmacology. Nat Rev Cancer. 2010;10(2):130–137.
   PubMed Web of Science ®Google Scholar
• Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355(23):2408–2417.
   PubMed Web of Science ®Google Scholar
• Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003;21(23):4342–4349.
   PubMed Web of Science ®Google Scholar
• Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and Safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344(14):1031–1037.
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon Alfa in metastatic renal-cell carcinoma. N Engl J Med. 2012;22(2):407–417.
   Google Scholar
• Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356:125–134.
   PubMed Web of Science ®Google Scholar
• Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti–vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003;349:427–434.
   PubMed Web of Science ®Google Scholar
• Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non–small-cell lung cancer. N Engl J Med. 2011;333(2):1109–1112.
   Google Scholar
• Sandler A, Gray R, Perry MC, et al. Paclitaxel–carboplatin alone or with bevacizumab for non–small-cell lung cancer. N Engl J Med. 2006;355(24):2542–2550.
   PubMed Web of Science ®Google Scholar
• Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2004;10(26):29–38.
   Google Scholar
• Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357(26):2666–2676.
   PubMed Web of Science ®Google Scholar
• Jonker DJ, O’Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007;357(20):2040–2048.
   PubMed Web of Science ®Google Scholar
• Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the national cancer institute of Canada clinical trials group. J Clin Oncol. 2007;25(15):1960–1966. .
   PubMed Web of Science ®Google Scholar
• Nimeiri HS, Oza AM, Morgan RJ, et al. A phase II study of sorafenib in advanced uterine carcinoma/carcinosarcoma: A trial of the Chicago, PMH, and California Phase II Consortia. Gynecol Oncol. 2010;117(1):37–40.
   PubMed Web of Science ®Google Scholar
• Bruix J, Sherman M. American association for the study of liver diseases. management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–1022.
   PubMed Web of Science ®Google Scholar
• Kamat AA, Merritt WM, Coffey D, et al. Clinical and biological significance of vascular endothelial growth factor in endometrial cancer. Clin Cancer Res. 2007;13(24):7487–7495.
   PubMed Web of Science ®Google Scholar
• McMeekin DS, Sill MW, Darcy KM, et al. A phase II trial of thalidomide in patients with refractory leiomyosarcoma of the uterus and correlation with biomarkers of angiogenesis: A gynecologic oncology group study. Gynecol Oncol. 2007;106(3):596–603.
   PubMed Web of Science ®Google Scholar
• Ninomiya Y. K-Ras and H-Ras activation promote distinct consequences on endometrial cell survival. Cancer Res. 2004;64(8):2759–2765.
   PubMed Web of Science ®Google Scholar
• Eritja N, Chen B-J, Rodríguez-Barrueco R, et al. Autophagy orchestrates adaptive responses to targeted therapy in endometrial cancer. Autophagy. 2017;13(3):608–624.
   PubMed Web of Science ®Google Scholar
• Llobet D, Eritja N, Yeramian A, et al. The multikinase inhibitor Sorafenib induces apoptosis and sensitises endometrial cancer cells to TRAIL by different mechanisms. Eur J Cancer. 2010;46(4):836–850.
   PubMed Web of Science ®Google Scholar
• Conza D, Mirra P, Calì G, et al. The SGK1 inhibitor SI113 induces autophagy, apoptosis, and endoplasmic reticulum stress in endometrial cancer cells. J Cell Physiol. 2017;232:3735–3743.
   PubMed Web of Science ®Google Scholar
• García-Martínez JM, Alessi DR. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J. 1985;20(3):113–129.
   Google Scholar
• Perrotti N, He RA, Phillips SA, et al. Activation of serum- and glucocorticoid-induced protein kinase (Sgk) by Cyclic AMP and Insulin. J Biol Chem. 2019;20(12):9406–9412.
   Google Scholar
• Bruhn MA, Pearson RB, Hannan RD, et al. Second AKT: the rise of SGK in cancer signalling. Growth Factors. 2010;28(6):394–408.
   PubMed Web of Science ®Google Scholar
• Lang F, Shumilina E. Regulation of ion channels by the serum- and glucocorticoid-inducible kinase SGK1. Faseb J. 2015;14(1):3–12.
   Google Scholar
• Kondratskyi A. Calcium-permeable ion channels in control of autophagy and cancer. Front Physiol. 2010;27:272.
   Google Scholar
• Filippi-Chiela EC, Viegas MS, Thome MP, et al. Modulation of autophagy by calcium signalosome in human disease. Mol Pharmacol. 2018;68(3):7–30.
   Google Scholar
• Bao -X-X, Xie B-S, Li Q, et al. Nifedipine induced autophagy through Beclin1 and mTOR pathway in endometrial carcinoma cells. Chin Med J. 2014;464(17):315–331.
   Google Scholar
• Fukuda T, Oda K, Wada-Hiraike O, et al. The novel estrogen-induced gene EIG121 regulates autophagy and promotes cell survival under stress. Oncol Lett. 2007;25(4):2983–2990. .
   Google Scholar
• Haraguchi H, Ishikawa H, Mizutani K, et al. Antioxidative and superoxide scavenging activities of retrochalcones in Glycyrrhiza inflata. Bioorg Med Chem. 1998;6:339–347.
   PubMed Web of Science ®Google Scholar
• Tawata M, Aida K, Noguchi T, et al. Anti-platelet action of isoliquiritigenin, an aldose reductase inhibitor in licorice. Eur J Pharmacol. 2008;18(1):87–92.
   Google Scholar
• Tamir S, Eizenberg M, Somjen D, et al. Estrogen-like activity of glabrene and other constituents isolated from licorice root. J Steroid Biochem Mol Biol. 2018;18(3):291–298.
   Google Scholar
• Li T, Satomi Y, Katoh D, et al. Induction of cell cycle arrest and p21CIP1/WAF1 expression in human lung cancer cells by isoliquiritigenin. Cancer Lett. 2004;207:27–35.
   PubMed Web of Science ®Google Scholar
• Wu C-H, Chen H-Y, Wang C-W, et al. Isoliquiritigenin induces apoptosis and autophagy and inhibits endometrial cancer growth in mice. Oncotarget. 2016;7(45):73432–73447.
   PubMedGoogle Scholar
• Li L, Wang ZV, Hill JA, et al. New autophagy reporter mice reveal dynamics of proximal tubular autophagy. J Am Soc Nephrol. 2001;276(2):9406–9412.
   Google Scholar
• Kaizuka T, Morishita H, Hama Y, et al. An autophagic flux probe that releases an internal control. Mol Cell. 2016;64:835–849.
   PubMed Web of Science ®Google Scholar
• Amaravadi RK, Kimmelman AC, Debnath J. Targeting autophagy in cancer: recent advances and future directions. Cancer Discov. 2019;9:1167–1181.
   PubMed Web of Science ®Google Scholar
• Pasquier B. SAR405, a PIK3C3/Vps34 inhibitor that prevents autophagy and synergizes with MTOR inhibition in tumor cells. Autophagy. 2015;11:725–726.
   PubMed Web of Science ®Google Scholar
• Ronan B, Flamand O, Vescovi L, et al. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol. 2014;10:1013–1019.
   PubMed Web of Science ®Google Scholar
• Pasquier B, El-Ahmad Y, Filoche-Rommé B, et al. Discovery of (2 S)-8-[(3 R)-3-Methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2 H -pyrimido[1,2- a]pyrimidin-6-one: A Novel Potent and Selective Inhibitor of Vps34 for the treatment of solid tumors. J Med Chem. 2015;58:376–400.
   PubMed Web of Science ®Google Scholar
• Dyczynski M, Yu Y, Otrocka M, et al. Targeting autophagy by small molecule inhibitors of vacuolar protein sorting 34 (Vps34) improves the sensitivity of breast cancer cells to Sunitinib. Cancer Lett. 2018;435:32–43.
   PubMed Web of Science ®Google Scholar
• Egan DF, Chun MGH, Vamos M, et al. Small molecule inhibition of the autophagy kinase ULK1 and identification of ULK1 substrates. Mol Cell. 2015;59:285–297.
   PubMed Web of Science ®Google Scholar
• Martin KR, Celano SL, Solitro AR, et al. A potent and selective ULK1 inhibitor suppresses autophagy and sensitizes cancer cells to nutrient stress. iScience. 2018;8:74–84.
   PubMed Web of Science ®Google Scholar
• Sharma G, Guardia CM, Roy A, et al. A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt multiple events in lysosome homeostasis. Autophagy. 2019;15:1694–1718.
   PubMed Web of Science ®Google Scholar
• Gayle S, Landrette S, Beeharry N, et al. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017;129:1768–1778.
   PubMed Web of Science ®Google Scholar