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.

• Authors: Hongping Xia, Shik Nie Kong, Jianxiang Chen, Ming Shi, Karthik Sekar, Veerabrahma Pratap Seshachalam, Muthukumar Rajasekaran, Brian Kim Poh Goh, London Lucien Ooi, Kam M Hui
• Journal: Cancer letters (Cancer Lett) Vol. 383 Issue 1 Pg. 85-93 (12 01 2016) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 27693640 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Chemical References

• FOXM1 protein, human
• Forkhead Box Protein M1
• MELK protein, human
• Protein Serine-Threonine Kinases

Topics

• Animals
• Apoptosis
• Carcinoma, Hepatocellular (enzymology, genetics, pathology, therapy)
• Cell Line, Tumor
• Cell Movement
• Cell Self Renewal
• Female
• Forkhead Box Protein M1 (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (enzymology, genetics, pathology, therapy)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Mitosis
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local
• Neoplastic Stem Cells (enzymology, pathology)
• Phenotype
• Protein Serine-Threonine Kinases (genetics, metabolism)
• RNA Interference
• Signal Transduction
• Time Factors
• Transfection
• Treatment Outcome
• Up-Regulation