p19Arf inhibits the invasion of hepatocellular carcinoma cells by binding to C-terminal binding protein
Document Type
Journal ArticlePublication Date
2008-01-18Keywords
3T3-L1 CellsAlcohol Oxidoreductases
Animals
Carcinoma, Hepatocellular
Cyclin-Dependent Kinase Inhibitor p16
inhibitors
DNA-Binding Proteins
Genes, Tumor Suppressor
Liver Neoplasms
Mice
Neoplasm Invasiveness
Protein Binding
Protein Interaction Domains and Motifs
RNA, Small Interfering
Tumor Cells, Cultured
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The INK4A/ARF tumor suppressor locus is frequently inactivated in hepatocellular carcinoma (HCC), yet the consequences of this remain unknown. We recently described a HCC mouse model in which loss of the Ink4a/Arf locus accelerates the development of metastasis and enhances tumor cell migration and invasion in cell culture assays. We show here that knockdown of p19Arf in an HCC cell line increases invasion in cell culture assays. Furthermore, reintroduction of p19(Arf) into HCC cell lines lacking Ink4a/Arf inhibits tumor cell invasion, without affecting cell proliferation, or cell transformation as measured by soft agar colony formation. Inhibition of cell invasion by p19(Arf) was dependent on its C-terminal binding protein (CtBP) interaction domain but independent of Mdm2 binding and nucleolar localization. Indeed, RNA interference-mediated knockdown of CtBP1 or CtBP2 decreased cell invasion, and ectopic expression of CtBP2 enhanced tumor cell migration and invasion. Thus, our data indicate a novel role for the Arf tumor suppressor protein in regulating phenotypes associated with tumor progression and metastasis in HCC cells.Source
Cancer Res. 2008 Jan 15;68(2):476-82. Link to article on publisher's site
DOI
10.1158/0008-5472.CAN-07-1960Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39101PubMed ID
18199542Related Resources
ae974a485f413a2113503eed53cd6c53
10.1158/0008-5472.CAN-07-1960