Flot2 promotes tumor growth and metastasis through modulating cell cycle and inducing epithelial-mesenchymal transition of hepatocellular carcinoma.

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Flot2 promotes tumor growth and metastasis through modulating cell cycle and inducing epithelial-mesenchymal transition of hepatocellular carcinoma.

Am J Cancer Res. 2017;7(5):1068-1083

Authors: Wang CH, Zhu XD, Ma DN, Sun HC, Gao DM, Zhang N, Qin CD, Zhang YY, Ye BG, Cai H, Shi WK, Cao MQ, Tang ZY

Abstract
Flotillin-2 (Flot2) is a highly conserved and ubiquitously expressed protein that resides on the cytoplasmic side of the cell membrane within specific cholesterol rich microdomains. Some studies have reported that overexpression of Flot2 is related to cancer progression. However, the role of Flot2 in hepatocellular carcinoma (HCC) remains unclarified. In this study, we aim to explore the correlation between Flot2 expression and HCC progression and the underlying mechanism. In the present study, overexpression of Flot2 in HCC tissues and cell lines was detected, and forced overexpression of Flot2 significantly promoted the proliferation, migration, invasion and metastasis of HCC in vitro and in vivo by modulating cell cycle and inducing EMT, which was mediated via up-regulation of Twist as a result of Raf/MEK/ERK1/2 pathway activation. In contrast, silencing Flot2 expression inhibited these biological processes. Furthermore, high expression of Flot2 was significantly correlated with poor prognosis of HCC patients after curative resection and is an independent risk factor. In conclusion, Flot2 promoted tumor growth and metastasis of HCC through modulating cell cycle and inducing EMT. The expression of Flot2 may play a key role in HCC progression and may be regarded as a potential poor prognostic marker for HCC.

PMID: 28560058 [PubMed]

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