DLC1 is a chromosome 8p tumor suppressor whose loss promotes hepatocellular carcinoma

Xue, W., Krasnitz, A., Lucito, R., Sordella, R., Van Aelst, L., Cordon-Cardo, C., Singer, S., Kuehnel, F., Wigler, M. H., Powers, S., Zender, L., Lowe, S. W. (2008) DLC1 is a chromosome 8p tumor suppressor whose loss promotes hepatocellular carcinoma. Genes & Development, 22 (11). pp. 1439-44. ISSN 0890-9369

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URL: http://www.ncbi.nlm.nih.gov/pubmed/18519636
DOI: 10.1101/gad.1672608

Abstract

Deletions on chromosome 8p are common in human tumors, suggesting that one or more tumor suppressor genes reside in this region. Deleted in Liver Cancer 1 (DLC1) encodes a Rho-GTPase activating protein and is a candidate 8p tumor suppressor. We show that DLC1 knockdown cooperates with Myc to promote hepatocellular carcinoma in mice, and that reintroduction of wild-type DLC1 into hepatoma cells with low DLC1 levels suppresses tumor growth in situ. Cells with reduced DLC1 protein contain increased GTP-bound RhoA, and enforced expression a constitutively activated RhoA allele mimics DLC1 loss in promoting hepatocellular carcinogenesis. Conversely, down-regulation of RhoA selectively inhibits tumor growth of hepatoma cells with disabled DLC1. Our data validate DLC1 as a potent tumor suppressor gene and suggest that its loss creates a dependence on the RhoA pathway that may be targeted therapeutically.

Item Type: Paper
Uncontrolled Keywords: DLC1 HCC RNAi RhoA mouse model
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 > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
diseases & disorders > cancer > cancer types > liver cancer
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Krasnitz lab
CSHL labs > Lowe lab
CSHL labs > Lucito lab
CSHL labs > Powers lab
CSHL labs > Sordella lab
CSHL labs > Van Aelst lab
CSHL labs > Wigler lab
Depositing User: Brian Soldo
Date Deposited: 28 Mar 2012 18:29
Last Modified: 13 Mar 2013 15:37
PMCID: PMC2418580
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25540

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