YAP overexpression promotes the epithelial-mesenchymal transition and chemoresistance in pancreatic cancer cells

Abstract

The expression of Yes-associated protein (YAP) has been reported to be dysregulated in pancreatic cancer. However, its contributions to tumor formation and progression remain to be elucidated. The present study demonstrated that YAP overexpression promoted the epithelial‑mesenchymal transition (EMT) in a manner associated with pancreatic cancer invasion in vitro. RNA interference‑mediated silencing of YAP attenuated cell invasion in vitro. Mechanistically, the present study demonstrated that YAP overexpression fosters pancreatic cancer progression by inducing the EMT in pancreatic cancer cells by activating the AKT cascade, which can counteract the effect of gemcitabine. These data suggested that the YAP acts synergistically to promote pancreatic cancer progression by hyperactivation of AKT signaling. The present study revealed YAP as a potential therapeutic target for pancreatic cancer and a biomarker for predicting gemcitabine treatment response.

Circulating lncRNA SNHG11 as a novel biomarker for early diagnosis and prognosis of colorectal cancer

“…In addition, YAP has been identified as a driver gene for EMT, which may contribute to the invasion and metastasis of cancers, 20,35 including gastric cancer, 36 breast cancer 37 and pancreatic cancer. [38][39][40] The results of the present study conclusively demonstrate that the SNHG11-induced malignant behaviour of CRC is accompanied by alterations in YAP phosphorylation and total YAP protein levels. SNHG11 abolishes the kinase activity of MST1 and MST2 and consequently leads to hypophosphorylation of Lats1 and YAP.…”

“…reported that YAP expression was highest in HCT116, LS174T, LoVo, SW480 and SW620 colon cancer cell lines and that the capacity of these cells for proliferation, metastasis and invasion was markedly reduced by silencing YAP expression. In addition, YAP has been identified as a driver gene for EMT, which may contribute to the invasion and metastasis of cancers, including gastric cancer, breast cancer and pancreatic cancer . The results of the present study conclusively demonstrate that the SNHG11‐induced malignant behaviour of CRC is accompanied by alterations in YAP phosphorylation and total YAP protein levels.…”

Pan‐cancer survey of epithelial–mesenchymal transition markers across the Cancer Genome Atlas

“…HIF1A and hypoxia regulate EMT in cancer (Tsai and Wu, 2012; Kao et al, 2016). Recently, YAP1 has been found to transcriptionally regulate EMT in various cancer types (Shao et al, 2014; Selth et al, 2016; Yuan et al, 2016). Wnt/β-catenin pathway (represented by CTNNB1, LEF1, TCF4 , etc.)…”

WWC2 is an independent prognostic factor and prevents invasion via Hippo signalling in hepatocellular carcinoma

“…Previous studies identified YAP was an independent prognostic marker, and inactivation of the Hippo pathway was significantly associated with poorer prognosis in HCC [12]. Moreover, overexpression of YAP induces the epithelialmesenchymal transition (EMT), growth factor-independent cell proliferation and oncogenesis [13][14][15]. In mammals, several tumour suppressors (Mst1/2, Sav1/WW45, Lats1/2, Mob1) regulate the transcriptional co-activator YAP, forming a kinase cascade that culminates in phosphorylation and inactivation of YAP [16][17][18].…”