Expression of YAP in endometrial carcinoma tissues and its effect on epithelial to mesenchymal transition

Abstract

Background: Yes-associated protein (YAP) can function as a cancer suppressor or a cancer promoter.Studies have proved that YAP can collaborate with other genes to accelerate cancerous epithelial to mesenchymal transition (EMT), but little is known about how YAP performs in endometrial carcinoma (EC).Methods: Real time-polymerase chain reaction (RT-PCR) and western blot (WB) were used to quantify the relative mRNA and protein levels of YAP in 50 EC tissue samples and 20 normal endometrial tissues in the proliferative phase. The association between YAP expression level and EC index (clinical stage, histologic grade, and lymphatic metastasis) was analyzed. YAP interference and overexpression vectors were constructed. RT-PCR and WB were used to quantify the mRNA and protein levels of YAP and EMT markers in the normal control group (N), the negative control group (NC), and the YAP interference and overexpression group. Cell counting kit-8 (CCK8) assay and scratch test were performed to evaluate the proliferation, invasion, and migration of EC cells after YAP interference and overexpression. Results:The mRNA and protein levels of YAP increased in EC tissues (P<0.01) and showed differences associated with histologic grade and lymphatic metastasis, not with the clinical stage (P>0.01). CCK8 assay showed that the proliferation of EC cells was inhibited after YAP interference and increased after YAP overexpression. The cell wound healing test displayed that the migration of EC cells was inhibited after YAP interference and increased after YAP overexpression. RT-PCR and WB found the mRNA and protein levels of E-cadherin (an EMT marker) increased (P<0.01), but those of other markers (N-cadherin, Vimentin) dropped (P<0.01) after YAP interference; however, these trends were inversed after YAP overexpression (P<0.01).Conclusions: YAP serves as an EC-promoting gene that may regulate the EMT and other EC-related processes via promoting the proliferation, invasion, and migration of EC cells.

Evaluation of Immunohistochemical Expression of Matrix Metallo-Proteinase14 (MMP14) in Endometrial Carcinoma Type I: Relation with β1- Integrin & Yes-Associated Protein 1(YAP1)

“…In the present study, YAP1 was correlated to higher grades of endometrial carcinoma with a significant statistical difference (P=0.001).These results were in consistent with Cheng et al (30) and Tsujiura et al (29) , YAP1 was also correlated to LVI (P<0.001), which was similar to Tsujiura et al (29) .…”

“…We documented in our study increased expression of YAP1 in EC (65.4%) indicating the role of YAP1 in cancer promotion. This was in line with Tsujiura et al (29) and Cheng et al (30) in EC cases and Bouvier et al (31) in their studies upon osteosarcoma cases.…”

“…These findings suggest the possible role of YAP1 in the invasion and progression of EC through MMP 14. This coincidences with Cheng et al (30) in their study on EC and Zhai et al (20) in their study on glioma. This could be explained through MMP14 mainly affects the nuclear localization of YAP1…”

O‑GlcNAcylation mediates endometrial cancer progression by regulating the Hippo‑YAP pathway

“…In EC cells and tissues, YAP is upregulated and its expression is significantly associated with tumor grade, stage, post-operative recurrence/metastasis, and overall survival (35)(36)(37). As YAP expression and function are controlled by its phosphorylation (38), altering its phosphorylation affects the malignancy of a variety of tumors by influencing YAP activation and nucleation (39,40).…”

Ferroptosis: Opportunities and Challenges in Treating Endometrial Cancer

“…On one hand, YAP/TAZ directly induced the expression of SLC7A11; on the other hand, it sustained the protein stability of ATF4, which synergistically induced SLC7A11 expression to inhibit ferroptosis (Gao et al, 2021). Moreover, Wu et al (2019) reported that the NF2-YAP signaling pathway played an important role on ferroptosis suppression, while antagonizing this signaling pathway contributed to ferroptosis through upregulating expression of Acyl-CoA Synthetase long-chain family member 4 (ACSL4) and TFRC The expression of YAP was higher in endometrial cancer than in the normal tissues and cells, which was associated with higher grade, stage, lympho-vascular space invasion, and postoperative recurrence/metastasis (Tsujiura et al, 2014;Cheng et al, 2020); the inhibition of YAP restrained proliferation, increasing therapy sensibility by reducing interleukin-6 (IL-6), IL-11, and IRS1 (Wang C. et al, 2016;Wang et al, 2019); and the knockdown of YAP and TAZ also prevented PI3K pathway activation by inhibiting the expression of GAB2 linker molecule in endometrial cancer (Wang et al, 2017).…”