Autophagy in the physiological endometrium and cancer.

ABSTRACT

Autophagy is a highly conserved catabolic process and a major cellular pathway for the degradation of long-lived proteins and cytoplasmic organelles. An increasing body of evidence has unveiled autophagy as an indispensable biological function that helps to maintain normal tissue homeostasis and metabolic fitness that can also lead to severe consequences for the normal cellular functioning when altered. Recent accumulating data point to autophagy as a key player in a wide variety of physiological and pathophysiological conditions in the human endometrium, one of the most proficient self-regenerating tissues in the human body and an instrumental player in placental species reproductive function. The current review highlights the most recent findings regarding the process of autophagy in the normal and cancerous endometrial tissue. Current research efforts aiming to therapeutically exploit autophagy and the methodological approaches used are discussed.Abbreviations 3-MA 3-methyladenine; ACACA (acetyl-CoA carboxylase alpha); AICAR 5-aminoimidazole-4-carboximide riboside; AKT AKT serine/threonine kinase; AMPK AMP-activated protein kinase; ATG autophagy related; ATG12 autophagy related 12; ATG16L1 autophagy related 16 like 1; ATG3 autophagy related 3; ATG4C autophagy related 4C cysteine peptidase; ATG5 autophagy related 5; ATG7 autophagy related 7; ATG9 autophagy related 9; Baf A1 bafilomycin A1; BAX BCL2 associated X, apoptosis regulator; BCL2 BCL2 apoptosis regulator; BECN1 beclin 1; CACNA1D calcium voltage-gated channel subunit alpha1 D; CASP3 caspase 3; CASP7 caspase 7; CASP8 caspase 8; CASP9 caspase 9; CD44 CD44 molecule (Indian blood group); CDH1 cadherin 1; CDKN1A cyclin dependent kinase inhibitor 1A; CDKN2A cyclin dependent kinase inhibitor 2A; CMA chaperone-mediated autophagy; CQ chloroquine; CTNNB1 catenin beta 1; DDIT3 DNA damage inducible transcript 3; EC endometrial cancer; EGFR epidermal growth factor receptor; EH endometrial hyperplasia; EIF4E eukaryotic translation initiation factor 4E; EPHB2/ERK EPH receptor B2; ER endoplasmic reticulum; ERBB2 er-b2 receptor tyrosine kinase 2; ERVW-1 endogenous retrovirus group W member 1, envelope; ESR1 estrogen receptor 1; FSH follicle-stimulating hormone; GCG/GLP1 glucagon; GFP green fluorescent protein; GIP gastric inhibitory polypeptide; GLP1R glucagon-like peptide-1 receptor; GLS glutaminase; H2AX H2A.X variant histone; HIF1A hypoxia inducible factor 1 alpha; HMGB1 high mobility group box 1; HOTAIR HOX transcript antisense RNA; HSPA5 heat shock protein family A (HSP70) member 5; HSPA8 heat shock protein family A (HSP70) member 8; IGF1 insulin like growth factor 1; IL27 interleukin 27; INS insulin; ISL isoliquiritigenin; KRAS KRAS proto-oncogene, GTPase; LAMP2 lysosomal-associated membrane protein 2; lncRNA long-non-coding RNA; MAP1LC3A/LC3A microtubule associated protein 1 light chain 3 alpha; MAP1LC3B/LC3B microtubule associated protein 1 light chain 3 beta; MAPK8 mitogen-activated protein kinase 8; MAPK9 mitogen-activated protein kinase 9; MPA medroxyprogesterone acetate; MTOR mechanistic target of rapamycin kinase; MTORC1 mechanistic target of rapamycin kinase complex 1; MTORC2 mechanistic target of rapamycin kinase complex 2; MYCBP MYC-binding protein; NFE2L2 nuclear factor, erythroid 2 like 2; NFKB nuclear factor kappa B; NFKBIA NFKB inhibitor alpha; NK natural killer; NR5A1 nuclear receptor subfamily 5 group A member 1; PARP1 poly(ADP-ribose) polymerase 1; PAX2 paired box 2; PDK1 pyruvate dehydrogenase kinase 1; PDX patient-derived xenograft; PIK3C3/Vps34 phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PIK3R1 phosphoinositide-3-kinase regulatory subunit 1; PIKFYVE phosphoinositide kinase, FYVE-type zinc finger containing; PPD protopanaxadiol; PRKCD protein kinase C delta; PROM1/CD133 prominin 1; PtdIns3K class III phosphatidylinositol 3-kinase; PtdIns3P phosphatidylinositol-3-phosphate; PTEN phosphatase and tensin homolog; RB1CC1/FIP200 RB1 inducible coiled-coil 1; RFP red fluorescent protein; RPS6KB1/S6K1 ribosomal protein S6 kinase B1; RSV resveratrol; SGK1 serum/glucocorticoid regulated kinase 1; SGK3 serum/glucocorticoid regulated kinase family member 3; SIRT sirtuin; SLS stone-like structures; SMAD2 SMAD family member 2; SMAD3 SMAD family member 3; SQSTM1 sequestosome 1; TALEN transcription activator-like effector nuclease; TGFBR2 transforming growth factor beta receptor 2; TP53 tumor protein p53; TRIB3 tribbles pseudokinase 3; ULK1 unc-51 like autophagy activating kinase 1; ULK4 unc-51 like kinase 4; VEGFA vascular endothelial growth factor A; WIPI2 WD repeat domain, phosphoinositide interacting 2; XBP1 X-box binding protein 1; ZFYVE1 zinc finger FYVE domain containing 1.