AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma

Xu, M. Z., Chan, S. W., Liu, A. M., Wong, K. F., Fan, S. T., Chen, J., Poon, R. T., Zender, L., Lowe, S. W., Hong, W., Luk, J. M. (March 2011) AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma. Oncogene, 30 (10). pp. 1229-1240.

URL: http://www.ncbi.nlm.nih.gov/pubmed/21076472
DOI: 10.1038/onc.2010.504

Abstract

Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC.Oncogene advance online publication, 15 November 2010; doi:10.1038/onc.2010.504.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
diseases & disorders > cancer > cancer types > liver cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL labs > Lowe lab
CSHL Cancer Center Program > Cancer Genetics
Depositing User: CSHL Librarian
Date: March 2011
Date Deposited: 19 Oct 2011 18:31
Last Modified: 15 Oct 2015 15:15
PMCID: PMC3330262
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15591

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