Laboratory of Precision Medicine, Oncobell Program. Bellvitge Biomedical Research Institute (IDIBELL), Gran via De l'Hospitalet, Barcelona, Spain.
Department of Pathology-Hospital Universitari Arnau De Vilanova, Universitat De Lleida, IRBLLEIDA, CIBERONC, Lleida, Spain.
Autophagy. 2021 May;17(5):1077-1095. doi: 10.1080/15548627.2020.1752548. Epub 2020 May 13.
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. 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 A; 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.
自噬是一种高度保守的分解代谢过程，是降解长寿蛋白和细胞质细胞器的主要细胞途径。越来越多的证据表明，自噬是一种必不可少的生物学功能，有助于维持正常的组织动态平衡和代谢适应，当自噬改变时，也会对正常的细胞功能产生严重后果。最近积累的数据表明，自噬是人类子宫内膜中多种生理和病理生理状况的关键参与者，子宫内膜是人体中最具自我再生能力的组织之一，也是胎盘物种生殖功能的重要参与者。本综述强调了自噬在正常和癌性子宫内膜组织中的最新发现。目前旨在通过自噬治疗的研究努力和所使用的方法学方法正在讨论中。3-MA：3-甲基腺嘌呤；ACACA（乙酰辅酶 A 羧化酶 alpha）；AICAR：5-氨基咪唑-4-羧基酰胺核苷；AKT：AKT 丝氨酸/苏氨酸激酶；AMPK：AMP 激活的蛋白激酶；ATG：自噬相关；ATG12：自噬相关 12；ATG16L1：自噬相关 16 样 1；ATG3：自噬相关 3；ATG4C：自噬相关 4C 半胱氨酸肽酶；ATG5：自噬相关 5；ATG7：自噬相关 7；ATG9：自噬相关 9；巴弗霉素 A1：巴弗霉素 A；BAX：BCL2 相关 X，凋亡调节剂；BCL2：BCL2 凋亡调节剂；BECN1：beclin 1；CACNA1D：钙电压门控通道亚基 alpha1 D；CASP3：半胱天冬酶 3；CASP7：半胱天冬酶 7；CASP8：半胱天冬酶 8；CASP9：半胱天冬酶 9；CD44：CD44 分子（印度血型）；CDH1：钙粘蛋白 1；CDKN1A：细胞周期蛋白依赖性激酶抑制剂 1A；CDKN2A：细胞周期蛋白依赖性激酶抑制剂 2A；CMA：伴侣介导的自噬；CQ：氯喹；CTNNB1：连环蛋白 beta 1；DDIT3：DNA 损伤诱导转录物 3；EC：子宫内膜癌；EGFR：表皮生长因子受体；EH：子宫内膜增生；EIF4E：真核翻译起始因子 4E；EPHB2/ERK：EPH 受体 B2；ER：内质网；ERBB2：表皮生长因子受体 2；ERVW-1：内源性逆转录病毒组 W 成员 1，包膜；ESR1：雌激素受体 1；FSH：卵泡刺激素；GCG/GLP1：胰高血糖素；GFP：绿色荧光蛋白；GIP：胃抑制多肽；GLP1R：胰高血糖素样肽-1 受体；GLS：谷氨酰胺酶；H2AX：H2A.X 变体组蛋白；HIF1A：缺氧诱导因子 1 alpha；HMGB1：高迁移率族盒 1；HOTAIR：HOX 转录反义 RNA；HSPA5：热休克蛋白家族 A（HSP70）成员 5；HSPA8：热休克蛋白家族 A（HSP70）成员 8；IGF1：胰岛素样生长因子 1；IL27：白细胞介素 27；INS：胰岛素；ISL：异甘草素；KRAS：KRAS 原癌基因，GTP 酶；LAMP2：溶酶体相关膜蛋白 2；lncRNA：长非编码 RNA；MAP1LC3A/LC3A：微管相关蛋白 1 轻链 3 alpha；MAP1LC3B/LC3B：微管相关蛋白 1 轻链 3 beta；MAPK8：有丝分裂原激活的蛋白激酶 8；MAPK9：有丝分裂原激活的蛋白激酶 9；MPA：醋酸甲地孕酮；MTOR：雷帕霉素靶蛋白激酶；MTORC1：雷帕霉素靶蛋白激酶复合物 1；MTORC2：雷帕霉素靶蛋白激酶复合物 2；MYCBP：MYC 结合蛋白；NFE2L2：核因子，红细胞 2 样 2；NFKB：核因子 kappa B；NFKBIA：NFKB 抑制剂 alpha；NK：自然杀伤细胞；NR5A1：核受体亚家族 5 组 A 成员 1；PARP1：多聚（ADP-核糖）聚合酶 1；PAX2：配对盒 2；PDK1：丙酮酸脱氢酶激酶 1；PDX：患者衍生的异种移植物；PI3K3/Vps34：磷脂酰肌醇 3-激酶催化亚基 3 型；PI3KCA：磷酸肌醇-4,5-二磷酸 3-激酶催化亚基 alpha；PIK3R1：磷酸肌醇-3-激酶调节亚基 1；PIKFYVE：磷酸肌醇激酶，FYVE 型锌指结构域包含；PPD：原人参二醇；PRKCD：蛋白激酶 C delta；PROM1/CD133：prominin 1；PtdIns3K：III 类磷酸肌醇 3-激酶；PtdIns3P：磷脂酰肌醇-3-磷酸；PTEN：磷酸酶和张力蛋白同源物；RB1CC1/FIP200：RB1 诱导卷曲螺旋 1；RFP：红色荧光蛋白；RPS6KB1/S6K1：核糖体蛋白 S6 激酶 B1；RSV：白藜芦醇；SGK1：血清/糖皮质激素调节激酶 1；SGK3：血清/糖皮质激素调节激酶家族成员 3；SIRT：沉默调节蛋白；SLS：石样结构；SMAD2：SMAD 家族成员 2；SMAD3：SMAD 家族成员 3；SQSTM1：自噬相关蛋白 1；TALEN：转录激活样效应物核酸酶；TGFBR2：转化生长因子 beta 受体 2；TP53：肿瘤蛋白 p53；TRIB3：tribbles 假激酶 3；ULK1：UNC-51 样自噬激活激酶 1；ULK4：UNC-51 样激酶 4；VEGFA：血管内皮生长因子 A；WIPI2：WD 重复域，磷酸肌醇相互作用 2；XBP1：X 盒结合蛋白 1；ZFYVE1：锌指 FYVE 结构域包含 1。
