MFGE8 regulates TGF-β-induced epithelial mesenchymal transition in endometrial epithelial cells in vitro

Yu, Lian; Hu, Rong; Sullivan, Claretta J.; Swanson, R. James; Oehninger, Sergio; Sun, Yingpu; Bocca, Silvina

doi:10.1530/rep-15-0585

Cited by 24 publications

(13 citation statements)

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“…TGF-β signaling has two major functions—the activation of SMAD signaling and non-SMAD pathways. Several non-SMAD signaling pathways have been implicated in the response to the full EMT process, including the PI3K/AKT, Ras/Raf/MEK/ERK, and Wnt/β-catenin signaling pathways (Figure 1) [116,117]. TGF-β interacts with the TGF-β receptor type I membrane receptor to phosphorylate the adaptor protein SRC homology 2 domain-containing-transforming A (SHCA).…”

Section: Epithelial-mesenchymal Transition (Emt) Signaling Pathwaymentioning

confidence: 99%

Epithelial to Mesenchymal Transition and Cell Biology of Molecular Regulation in Endometrial Carcinogenesis

Chiu

Yiang

et al. 2019

JCM

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Endometrial carcinogenesis is involved in several signaling pathways and it comprises multiple steps. The four major signaling pathways—PI3K/AKT, Ras/Raf/MEK/ERK, WNT/β-catenin, and vascular endothelial growth factor (VEGF)—are involved in tumor cell metabolism, growth, proliferation, survival, and angiogenesis. The genetic mutation and germline mitochondrial DNA mutations also impair cell proliferation, anti-apoptosis signaling, and epithelial–mesenchymal transition by several transcription factors, leading to endometrial carcinogenesis and distant metastasis. The PI3K/AKT pathway activates the ransforming growth factor beta (TGF-β)-mediated endothelial-to-mesenchymal transition (EMT) and it interacts with downstream signals to upregulate EMT-associated factors. Estrogen and progesterone signaling in EMT also play key roles in the prognosis of endometrial carcinogenesis. In this review article, we summarize the current clinical and basic research efforts regarding the detailed molecular regulation in endometrial carcinogenesis, especially in EMT, to provide novel targets for further anti-carcinogenesis treatment.

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Section: Epithelial-mesenchymal Transition (Emt) Signaling Pathwaymentioning

confidence: 99%

Epithelial to Mesenchymal Transition and Cell Biology of Molecular Regulation in Endometrial Carcinogenesis

Chiu

Yiang

et al. 2019

JCM

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“…In SMAD-mediated signaling, TGF-β directly binds to the membrane receptors, leading to the formation of the SMAD complex by activating SMAD2/3/4. In non-SMAD signaling pathways, TGF-β triggers the AKT/PI3K pathway, Ras/Raf/MEK/ERK signaling pathway, and Wnt/β-catenin signaling pathway in order to induce the expression of epithelial proteins [45,46]. Moreover, the TGF-β type I receptor interacts with the Src homology 2 domain-containing transforming protein 1 (SHC1) to activate the growth factor receptor-bound protein 2 (GRB2) and son of sevenless (SOS) in order to induce Ras/Raf/MEK/ERK signaling.…”

Section: The Role Of the Tgf-β Pathway In Breast Cancermentioning

confidence: 99%

The Molecular Mechanism of Epithelial–Mesenchymal Transition for Breast Carcinogenesis

Chu

Yiang

et al. 2019

Biomolecules

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The transforming growth factor-β (TGF-β) signaling pathway plays multiple regulatory roles in the tumorigenesis and development of cancer. TGF-β can inhibit the growth and proliferation of epithelial cells and induce apoptosis, thereby playing a role in inhibiting breast cancer. Therefore, the loss of response in epithelial cells that leads to the inhibition of cell proliferation due to TGF-β is a landmark event in tumorigenesis. As tumors progress, TGF-β can promote tumor cell invasion, metastasis, and drug resistance. At present, the above-mentioned role of TGF-β is related to the interaction of multiple signaling pathways in the cell, which can attenuate or abolish the inhibition of proliferation and apoptosis-promoting effects of TGF-β and enhance its promotion of tumor progression. This article focuses on the molecular mechanisms through which TGF-β interacts with multiple intracellular signaling pathways in tumor progression and the effects of these interactions on tumorigenesis.

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“…A recently published study using an in-vitro model of attachment showed that treatment with ovarian steroid hormones resulted in changes of N-cadherin, E-cadherin and vimentin (mesenchymal cell markers) in Ishikawa cells, accelerated Ishikawa cell motility and increased JAR spheroid outgrowth. This strongly suggested activation of EMT ( Uchida et al , 2012 ; Yu et al , 2016 ). The conclusion of these authors collectively suggested that the ovarian steroid hormones and the implanting embryo (Jar spheroids mimicking trophoblast) induced EMT of EECs, which may play a key role in early human embryo implantation.…”

Section: Discussionmentioning

confidence: 89%

Aquaporin-3 mediates ovarian steroid hormone-induced motility of endometrial epithelial cells

et al. 2018

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STUDY QUESTIONHow does aquaporin-3 (AQP3) affect endometrial receptivity?SUMMARY ANSWERAQP3, which is regulated by the combination and estrogen (E2) and progesterone (P4), induces epithelial–mesenchymal transition (EMT) of endometrial epithelial cells.WHAT IS KNOWN ALREADYEmbryo implantation is an extremely complex process, and endometrial receptivity is essential for successful embryo implantation. Estrogen and progesterone regulate endometrial receptivity. AQP3, which is regulated by estrogen (E2), increases cell migration and invasion ability by regulating the expression of EMT-related factors and influencing the reorganization of the actin cytoskeleton.STUDY DESIGN, SIZE, DURATIONThis study investigated the pathophysiological significance of AQP3 in human endometrial function during different phases of the menstrual cycle.PARTICIPANTS/MATERIALS, SETTING, METHODSAQP3 expression levels during different phases of the menstrual cycle were measured using immunohistochemical assays. In cells of different receptivity (high-receptive RL95-2 cells and low-receptive HEC-1A cells), the expression of AQP3 was measured using western blotting, qRT-PCR and immunofluorescence assays. Activities of AQP3, and its regulation by E2 and P4, were studied through in-vitro experiments using RL95-2 cells.MAIN RESULTS AND THE ROLE OF CHANCEAQP3 expression in the mid- and late-secretory phases of the human endometrium is significantly higher than in other phases. Since AQP3 expression levels were higher in RL95-2 cells than in HEC-1A cells, mechanisms of AQP3 regulation by E2 and P4 were studied using RL95-2 cells. We provided the first report that P4 up-regulates AQP3 by directly targeting the promoter of the AQP3 gene. The up-regulation of AQP3 expression by a combination of E2 and P4 is significantly higher than that caused by either E2 or P4 alone. Together E2 and P4 promote RL95-2 cell migration and invasion by inducing EMT through AQP3. We also found that AQP3 co-localizes with ezrin and affects the formation of filopodia and lamellipodia during the E2 and P4-induced EMT process but has no effect on the expression of ezrin and F-actin.LARGE SCALE DATAN/A.LIMITATIONS, REASONS FOR CAUTIONIt is still unclear whether AQP3 is a main regulator of endometrial receptivity or one of several factors influencing the process.WIDER IMPLICATIONS OF THE FINDINGSFurther investigation on AQP3 may contribute to a greater understanding of endometrial receptivity.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the National Natural Scientific Grants of China (No. 31570798), the Program for Liaoning Excellent Talents in University (LR2017042), the Doctoral Scientific Research Foundation of Liaoning province (201601236), and the Liaoning Provincial Program for Top Discipline of Basic Medical Sciences. There are no conflicts of interest.

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MFGE8 regulates TGF-β-induced epithelial mesenchymal transition in endometrial epithelial cells in vitro

Cited by 24 publications

References 50 publications

Epithelial to Mesenchymal Transition and Cell Biology of Molecular Regulation in Endometrial Carcinogenesis

Epithelial to Mesenchymal Transition and Cell Biology of Molecular Regulation in Endometrial Carcinogenesis

The Molecular Mechanism of Epithelial–Mesenchymal Transition for Breast Carcinogenesis

Aquaporin-3 mediates ovarian steroid hormone-induced motility of endometrial epithelial cells

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