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.
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: | https://repository.cshl.edu/id/eprint/15591 |
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