Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer

Yoriki, Kaori; Mori, Taisuke; Kokabu, Tetsuya; Miyata, Hiroshi; Umemura, Satoshi; Tarumi, Yosuke; Kitawaki, Jo

doi:10.1038/s41598-019-43261-z

Cited by 41 publications

(33 citation statements)

References 51 publications

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“…First, our results demonstrated that different concentrations of estrogen had different effects on normal endometrial epithelial cells, and relatively high doses of estrogen (30 nM) inhibited cell proliferation by promoting the progress of EMT in normal endometrium. Previous studies found that estrogen was sensitive to EMT progression in endometrial cancer and endometriosis ( 24 , 25 ). Since endometrial fibrosis is the main cause of IUA occurrence and poor prognosis, we further investigated the impact of the same dose of estrogen on EMT in the fibrotic environment.…”

Section: Discussionmentioning

confidence: 90%

Estrogen attenuates TGF-β1-induced EMT in intrauterine adhesion by activating Wnt/β-catenin signaling pathway

Cao

Liú

Zhao

et al. 2020

Braz J Med Biol Res

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Although estrogen has crucial functions for endometrium growth, the specific dose and underlying molecular mechanism in intrauterine adhesion (IUA) remain unclear. In this study, we aimed to investigate the effects of estrogen on epithelial-mesenchymal transition (EMT) in normal and fibrotic endometrium, and the role of estrogen and Wnt/β-catenin signaling in the formation of endometrial fibrosis. CCK-8 and immunofluorescence assay were performed to access the proliferation of different concentrations of estrogen on normal human endometrial epithelial cells (hEECs). qRT-PCR and western blot assay were utilized to explore the effect of estrogen on EMT in normal and fibrotic endometrium, and main components of Wnt/β-catenin signaling pathway in vitro . Hematoxylin and eosin and Masson staining were used to evaluate the effect of estrogen on endometrial morphology and fibrosis in vivo . Our results indicated that the proliferation of normal hEECs was inhibited by estrogen at a concentration of 30 nM accompanied by upregulation of mesenchymal markers and downregulation of epithelial markers. Interestingly, in the model of transforming growth factor β1 (TGF-β1)-induced endometrial fibrosis, the same concentration of estrogen inhibited the process of EMT, which might be partially mediated by regulation of the Wnt/β-catenin pathway. In addition, relatively high doses of estrogen efficiently increased the number of endometrial glands and reduced the area of fibrosis as determined by the reduction of EMT in IUA animal models. Taken together, our results demonstrated that an appropriate concentration of estrogen may prevent the occurrence and development of IUA by inhibiting the TGF-β1-induced EMT and activating the Wnt/β-catenin pathway.

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Section: Discussionmentioning

confidence: 90%

Estrogen attenuates TGF-β1-induced EMT in intrauterine adhesion by activating Wnt/β-catenin signaling pathway

Cao

Liú

Zhao

et al. 2020

Braz J Med Biol Res

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“…Some of these findings are reminiscent of results reported in breast cancer (BC), where ER down-regulates E-cadherin levels and fosters EMT process [65,66]. It is noteworthy that recent studies also reported a role for the nuclear orphan estrogen-related receptor alpha (ERR) in EMT and progression of lung [67] as well as endometrial [68] cancer cells.…”

Section: Estrogen Receptor (Er) α In Epithelial Mesenchymal Transimentioning

confidence: 85%

Estrogen Receptors in Epithelial-Mesenchymal Transition of Prostate Cancer

Zazzo

Galasso

Giovannelli

et al. 2019

Cancers

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Prostate cancer (PC) remains a widespread malignancy in men. Since the androgen/androgen receptor (AR) axis is associated with the pathogenesis of prostate cancer, suppression of AR-dependent signaling by androgen deprivation therapy (ADT) still represents the primary intervention for this disease. Despite the initial response, prostate cancer frequently develops resistance to ADT and progresses. As such, the disease becomes metastatic and few therapeutic options are available at this stage. Although the majority of studies are focused on the role of AR signaling, compelling evidence has shown that estrogens and their receptors control prostate cancer initiation and progression through a still debated mechanism. Epithelial versus mesenchymal transition (EMT) is involved in metastatic spread as well as drug-resistance of human cancers, and many studies on the role of this process in prostate cancer progression have been reported. We discuss here the findings on the role of estrogen/estrogen receptor (ER) axis in epithelial versus mesenchymal transition of prostate cancer cells. The pending questions concerning this issue are presented, together with the impact of the available data in clinical management of prostate cancer patients.

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“…In this regard, several studies have shown that Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), mammalian target of rapamycin (mTOR), and c-Myc pathways regulate biogenesis and mitochondrial activity in metastatic cells. These pathways are able to suppress the expression of E-cadherin, to stimulate the expression of epithelial–mesenchymal-transition-associated factors, such as vimentin and Snail, and also to positively regulate the Transforming Growth Factor-β1 (TGF-β1)-Induced EMT [ 21 , 22 , 23 , 24 ].…”

Section: Mitochondria and Cancermentioning

confidence: 99%

Targeting the Mitochondrial Metabolic Network: A Promising Strategy in Cancer Treatment

Frattaruolo

Brindisi

Curcio

et al. 2020

IJMS

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Metabolic reprogramming is a hallmark of cancer, which implements a profound metabolic rewiring in order to support a high proliferation rate and to ensure cell survival in its complex microenvironment. Although initial studies considered glycolysis as a crucial metabolic pathway in tumor metabolism reprogramming (i.e., the Warburg effect), recently, the critical role of mitochondria in oncogenesis, tumor progression, and neoplastic dissemination has emerged. In this report, we examined the main mitochondrial metabolic pathways that are altered in cancer, which play key roles in the different stages of tumor progression. Furthermore, we reviewed the function of important molecules inhibiting the main mitochondrial metabolic processes, which have been proven to be promising anticancer candidates in recent years. In particular, inhibitors of oxidative phosphorylation (OXPHOS), heme flux, the tricarboxylic acid cycle (TCA), glutaminolysis, mitochondrial dynamics, and biogenesis are discussed. The examined mitochondrial metabolic network inhibitors have produced interesting results in both preclinical and clinical studies, advancing cancer research and emphasizing that mitochondrial targeting may represent an effective anticancer strategy.

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Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer

Cited by 41 publications

References 51 publications

Estrogen attenuates TGF-β1-induced EMT in intrauterine adhesion by activating Wnt/β-catenin signaling pathway

Estrogen attenuates TGF-β1-induced EMT in intrauterine adhesion by activating Wnt/β-catenin signaling pathway

Estrogen Receptors in Epithelial-Mesenchymal Transition of Prostate Cancer

Targeting the Mitochondrial Metabolic Network: A Promising Strategy in Cancer Treatment

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