Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism

Zhou, Wen‐Jie; Zhang, Jie; Yang, Hui‐Li; Wu, Ke; Xie, Feng; Wu, Jiang‐Nan; Wang, Yan; Yao, Li; Zhuang, Yan; Xiang, Jianbin; Zhang, Aijun; He, Yongzhong; Li, Ming‐Qing

doi:10.1186/s12964-019-0412-9

Cited by 56 publications

(41 citation statements)

References 42 publications

(40 reference statements)

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“…Nevertheless, some insights can still be obtained from studies on autophagy in uterine corpus endometrial carcinoma (UCEC) cells. Consistent with estrogen's inhibitory effect on the autophagy of ESCs, our previous studies also show that estrogen significantly restricts autophagy of UCEC cells in vitro and in vivo 26 , 27 . Many drugs targeting autophagy-suppression are already in clinical use for endometrial hyperplasia 28 .…”

Section: Autophagy-related Molecules During the Menstruation Cyclesupporting

confidence: 74%

“…However, PPD downregulates the expression of ERα, upregulates the expression of progesterone receptors (PGRs), which restricts estrogen-mediated anti-autophagy effects in ESCs 38 . Moreover, fulvestrant is a selective ER antagonist that can abrogate the inhibitory effect of estrogen on autophagy in UCEC cells 26 .…”

Section: Autophagy-related Molecules During the Menstruation Cyclementioning

confidence: 99%

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Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis

et al. 2021

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Menstruation occurs in few species and involves a cyclic process of proliferation, breakdown and regeneration under the control of ovarian hormones. Knowledge of normal endometrial physiology, as it pertains to the regulation of menstruation, is essential to understand disorders of menstruation. Accumulating evidence indicates that autophagy in the endometrium, under the regulation of ovarian hormones, can result in the infiltration of immune cells, which plays an indispensable role in the endometrium shedding, tissue repair and prevention of infections during menstruation. In addition, abnormal autophagy levels, together with resulting dysregulated immune system function, are associated with the pathogenesis and progression of endometriosis. Considering its potential value of autophagy as a target for the treatment of menstrual-related and endometrium-related disorders, we review the activity and function of autophagy during menstrual cycles. The role of the estrogen/progesterone-autophagy-immunity axis in endometriosis are also discussed.

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Section: Autophagy-related Molecules During the Menstruation Cyclesupporting

confidence: 74%

Section: Autophagy-related Molecules During the Menstruation Cyclementioning

confidence: 99%

Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis

et al. 2021

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“…In the field of endometrial cancer research, it has been reported that isoliquiritigenin (ISL) can induce autophagy in endometrial cancer cells, thereby exerting a cancer-suppressing effect [ 29 ]. High levels of estrogen affect glutathione metabolism by increasing the level of glutaminase, thereby inhibiting autophagy in endometrial cancer and promoting its growth [ 30 ]. Kanda R, et al showed that glucagon-like peptide-1 receptor (GLP-1R) promotes autophagy in endometrial cancer, thereby inhibiting its growth and suggesting GLP-1R agonists as a potential therapeutic strategy [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

An integrated autophagy-related gene signature predicts prognosis in human endometrial Cancer

et al. 2020

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Background Globally, endometrial cancer is the fourth most common malignant tumor in women and the number of women being diagnosed is increasing. Tumor progression is strongly related to the cell survival-promoting functions of autophagy. We explored the relationship between endometrial cancer prognoses and the expression of autophagy genes using human autophagy databases. Methods The Cancer Genome Atlas was used to identify autophagy related genes (ARGs) that were differentially expressed in endometrial cancer tissue compared to healthy endometrial tissue. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were referenced to identify important biological functions and signaling pathways related to these differentially expressed ARGs. A prognostic model for endometrial cancer was constructed using univariate and multivariate Cox, and Least Absolute Shrinkage and Selection Operator regression analysis. Endometrial cancer patients were divided into high- and low-risk groups according to risk scores. Survival and receiver operating characteristic (ROC) curves were plotted for these patients to assess the accuracy of the prognostic model. Using immunohistochemistry the protein levels of the genes associated with risk were assessed. Results We determined 37 ARGs were differentially expressed between endometrial cancer and healthy tissues. These genes were enriched in the biological processes and signaling pathways related to autophagy. Four ARGs (CDKN2A, PTK6, ERBB2 and BIRC5) were selected to establish a prognostic model of endometrial cancer. Kaplan–Meier survival analysis suggested that high-risk groups have significantly shorter survival times than low-risk groups. The area under the ROC curve indicated that the prognostic model for survival prediction was relatively accurate. Immunohistochemistry suggested that among the four ARGs the protein levels of CDKN2A, PTK6, ERBB2, and BIRC5 were higher in endometrial cancer than healthy endometrial tissue. Conclusions Our prognostic model assessing four ARGs (CDKN2A, PTK6, ERBB2, and BIRC5) suggested their potential as independent predictive biomarkers and therapeutic targets for endometrial cancer.

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“…p62/Sqstm1 gene is a well-known autophagy marker (Gómez-Sánchez et al, 2016). Recent study showed that estrogen inhibits autophagy in endometrial cancer (Zhou et al, 2019). Neuroprotective effects of E2 in peripheral neurons are partly related to the suppression of excessive autophagy (Lin et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Effects of estrogen on fatty-acid-induced cytotoxicity in mouse Neuro-2a neural cells

Ogawa

Kyoya

Kimura

et al. 2020

Fundam. Toxicol. Sci.

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The accumulation of free fatty acids induces lipotoxicity in neural cells. Estrogen, 17βestradiol (E2) protects against the damage of cells in various organs and tissues. However, the role of E2 on lipotoxicity in neural cells remains unclear. In this study, we investigated the effects of E2 on stearic acid (saturated fatty acid)-and oleic acid (unsaturated fatty acid)-induced cytotoxicity in retinoic acid-induced mouse neuroblastoma Neuro-2a differentiated into neural cells. Cell viability was evaluated by lactate dehydrogenase release from Neuro-2a neural cells. Stearic acid and oleic acids suppressed the cell viability in a dose-dependent manner. E2 prevented oleic acid-induced cytotoxicity but had no effect on stearic acid-induced cytotoxicity. ERα-selective agonist prevented cytotoxicity in Neuro-2a neural cells. In contrast, ERβ-selective agonist slightly significantly enhanced the cytotoxicity in the presence of oleic acid. Oleic acid, but not stearic acid, increased the mRNA level of p62/Sqstm1. E2 treatment statistically significantly, but slightly, enhanced the stearic acid-induced Bax expression. In contrast, E2 and ERαselective agonist inhibited the oleic acid-induced the p62/Sqstm1 expression. Our results suggested that fatty acids induced cytotoxicity in Neuro-2a neural cells, and estrogen prevented the oleic acid-induced cytotoxicity via ERα, but not ERβ. Further studies are needed to understand the role of ERβ in neuron injury under normal conditions.

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Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism

Cited by 56 publications

References 42 publications

Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis

Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis

An integrated autophagy-related gene signature predicts prognosis in human endometrial Cancer

Effects of estrogen on fatty-acid-induced cytotoxicity in mouse Neuro-2a neural cells

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