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Transforming growth factor-beta1 suppresses hepatocellular carcinoma proliferation via activation of Hippo signaling.

ABSTRACT: In this study, we examined the expression of core proteins of the Hippo signaling pathway in hepatocellular carcinoma (HCC) cells treated with transforming growth factor-? 1(TGF-?1) and investigated the relationship between TGF-?1 and the Hippo signaling pathway, in order to better understand their roles in HCC and their potential implications for cancer therapy. We prove that the Hippo signaling pathway is involved in the TGF-?1-induced inhibition of the growth of HCC cells. Large tumor suppressor expression (LATS1) was overexpression and yes association protein 1(YAP1) translocated from the nucleus to the cytoplasm in HCC cells treated with TGF-?1. Overexpression of LATS1 and the nucleocytoplasmic translocation of YAP1 play an anti-oncogenetic role in the occurrence and development of liver cancer. Our findings provide new insight into strategies for liver cancer therapy.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5444703 | biostudies-other | 2017 May

REPOSITORIES: biostudies-other

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Transforming growth factor-beta1 suppresses hepatocellular carcinoma proliferation via activation of Hippo signaling.

Zhang Xiaodong X Fan Qing Q Li Yan Y Yang Zhaoguo Z Yang Liang L Zong Zhihong Z Wang Biao B Meng Xin X Li Qin Q Liu Jingang J Li Hangyu H

Oncotarget 20170501 18

In this study, we examined the expression of core proteins of the Hippo signaling pathway in hepatocellular carcinoma (HCC) cells treated with transforming growth factor-β 1(TGF-β1) and investigated the relationship between TGF-β1 and the Hippo signaling pathway, in order to better understand their roles in HCC and their potential implications for cancer therapy. We prove that the Hippo signaling pathway is involved in the TGF-β1-induced inhibition of the growth of HCC cells. Large tumor suppres ...[more]

PMID: 28076850

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Project description:Septin 6 (SEPT6) is a member of the GTP‑binding protein family that is highly conserved in eukaryotes and regulates various biological functions, including filament dynamics, cytokinesis and cell migration. However, the functional importance of SEPT6 in hepatocellular carcinoma (HCC) is not completely understood. The present study aimed to investigate the expression levels and roles of SEPT6 in HCC, as well as the underlying mechanisms. The reverse transcription quantitative PCR, western blotting and immunohistochemistry staining results demonstrated that SEPT6 expression was significantly elevated in HCC tissues compared with corresponding adjacent non‑tumor tissues, which indicated that SEPT6 expression may serve as a marker of poor prognosis for HCC. By performing plasmid transfection and G418 treatment, stable SEPT6‑knockdown and SEPT6‑overexpression cell lines were established. The Cell Counting Kit‑8, flow cytometry and Transwell assay results demonstrated that SEPT6 overexpression significantly increased HCC cell proliferation, cell cycle transition, migration and invasion compared with the Vector group, whereas SEPT6 knockdown displayed significant suppressive effects on HCC cell lines in vitro compared with the control group. Mechanistically, SEPT6 might facilitate F‑actin formation, which induced large tumor suppressor kinase 1 dephosphorylation, inhibited Hippo signaling, upregulated yes‑associated protein (YAP) expression and nuclear translocation, and upregulated cyclin D1 and matrix metallopeptidase 2 (MMP2) expression. Furthermore, YAP overexpression significantly reversed SEPT6 knockdown‑induced inhibitory effects on HCC, whereas YAP knockdown significantly inhibited the oncogenic effect of SEPT6 overexpression on HCC. Collectively, the present study demonstrated that SEPT6 may promote HCC progression by enhancing YAP activation, suggesting that targeting SEPT6 may serve as a novel therapeutic strategy for HCC.

Dataset Information

Transforming growth factor-beta1 suppresses hepatocellular carcinoma proliferation via activation of Hippo signaling.

Publications

Transforming growth factor-beta1 suppresses hepatocellular carcinoma proliferation via activation of Hippo signaling.

Similar Datasets

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