EMT induced by loss of LKB1 promotes migration and invasion of liver cancer cells through ZEB1‑induced YAP signaling

Qiu,Bijun; Wei,Wei; Zhu,Jianwen; Fu,Guangshun; Lu,Dahai

doi:10.3892/ol.2018.9445

EMT induced by loss of LKB1 promotes migration and invasion of liver cancer cells through ZEB1‑induced YAP signaling

Authors:
- Bijun Qiu
- Wei Wei
- Jianwen Zhu
- Guangshun Fu
- Dahai Lu
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Affiliations: General Surgery Department, Jiangdu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu 321088, P.R. China, Pathology Department, Hong Quan Hospital of Yangzhou, Yangzhou, Jiangsu 321088, P.R. China
Published online on: September 18, 2018 https://doi.org/10.3892/ol.2018.9445
Pages: 6465-6471
Copyright: © Qiu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver cancer cells often exhibit mesenchymal phenotypes, a critical phenotypic alteration of cancer cells termed the epithelial‑mesenchymal transition (EMT). To examine whether liver kinase B1 (LKB1) serves a potential role in EMT in liver carcinogenesis, in the present study, it was determined that the expression of LKB1 decreased in the hepatocellular carcinoma (HCC) cell line, compared with a normal liver cell line. LKB1 overexpression decreased cell motility and invasiveness. Furthermore, the loss of LKB1 induced the expression of several EMT marker proteins, including that of Zinc Finger E‑Box Binding Homeobox 1 (ZEB1). Notably, the expression of Yes‑associated protein (YAP) was positively associated with that of ZEB1 in LKB1‑knockdown cells with a mesenchymal phenotype. Here, we describe the direct regulation of the Hippo pathway effector YAP by ZEB1. The findings of the present study demonstrate that ZEB1 regulates the expression of YAP and regulates the expression of downstream target genes to promote malignant progression.

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