Activation of multiple cancer pathways and tumor maintenance function of the 3q amplified oncogene FNDC3B

Cai, C. L., Rajaram, M., Zhou, X., Liu, Q., Marchica, J., Li, J. Y., Powers, R. S. (May 2012) Activation of multiple cancer pathways and tumor maintenance function of the 3q amplified oncogene FNDC3B. Cell Cycle, 11 (9). pp. 1773-1781. ISSN 1538-4101

URL: http://www.ncbi.nlm.nih.gov/pubmed/22510613
DOI: 10.4161/cc.20121

Abstract

FNDC3B was recently identified in an oncogenomic screen for amplified oncogenes in hepatocellular carcinoma. It is located at 3q26 and is amplified in over 20% of cancers, usually as part of a broad amplified region encompassing the entire 3q arm. Consistent with an oncogenic role in multiple cancer types, we show here that overexpression of FNDC3B is capable of malignantly transforming mammary and kidney epithelial cells in addition to hepatocytes. To explore how FNDC3B transforms cells, we determined the cellular localization of its gene product and the cancer pathways that it activates. We found that the FNDC3B oncoprotein localizes to the Golgi network, and that its correct localization is essential for its transforming function. We found that overexpression of FNDC3B induces the epithelial-to-mesenchymal transition (EMT) and activates several cancer pathways, including PI3-kinase/Akt, Rb1 and TGF beta signaling. For TGF beta signaling, we analyzed the point in the pathway at which FNDC3B operates and obtained evidence that it induces expression of all three TGF beta ligands and also promotes TGFBR1 cell-surface localization. We found that RNAi-mediated knockdown of FNDC3B in cancer cells with 3q amplification suppressed their clonogenicity and tumorigenicity, but that the same RNAi knockdown had no effect on single-copy 3q cancer cells. These results indicate that FNDC3B is an important oncogenic driver gene of the 3q amplicon, adding to the growing list of oncogenic drivers within this commonly amplified region.

Item Type: Paper
Uncontrolled Keywords: amplification oncogene EMT tumor maintenance Golgi breast-cancer lung-cancer cell-lines liver-cancer gene fad104 amplification genome suppressor expression ovarian
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
CSHL Authors:
Communities: CSHL Post Doctoral Fellows
CSHL labs > Powers lab
CSHL Cancer Center Program > Cancer Genetics
Depositing User: Matt Covey
Date: May 2012
Date Deposited: 31 Jan 2013 21:00
Last Modified: 13 Oct 2015 19:50
PMCID: PMC3372389
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26913

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