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MELK is an oncogenic kinase essential for early hepatocellular carcinoma recurrence.

Abstract：

:Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Many kinases have been found to be intimately involved in oncogenesis and the deregulation of kinase function has emerged as a major mechanism by which cancer cells evade normal physiological constraints on growth and survival. Previously, we have performed gene expression profile analysis on HCC samples and have identified a host of kinases that are remarkably overexpressed in HCC. Among these, the Maternal Embryonic Leucine Zipper Kinase (MELK) is highly overexpressed in HCC and its overexpression strongly correlates with early recurrence and poor patients' survival. Silencing MELK inhibited cell growth, invasion, stemness and tumorigenicity of HCC cells by inducing apoptosis and mitosis. We further showed that the overexpression of MELK in HCC samples strongly correlated with the cell cycle- and mitosis-related genes which are directly regulated as part of the forkhead transcription factor FoxM1-related cell division program. Together, our data establish MELK as an oncogenic kinase involved in the pathogenesis and recurrence of HCC and could provide a promising molecular target to develop therapeutic strategies for patients with advanced HCC.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Xia H,Kong SN,Chen J,Shi M,Sekar K,Seshachalam VP,Rajasekaran M,Goh BKP,Ooi LL,Hui KM

doi

10.1016/j.canlet.2016.09.017

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

85-93

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(16)30559-6

journal_volume

383

pub_type

杂志文章

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