Title

p19Arf inhibits the invasion of hepatocellular carcinoma cells by binding to C-terminal binding protein

UMMS Affiliation

Program in Gene Function and Expression; Department of Cancer Biology

Publication Date

1-18-2008

Document Type

Article

Subjects

3T3-L1 Cells; Alcohol 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

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Cancer Res. 2008 Jan 15;68(2):476-82. Link to article on publisher's site

DOI of Published Version

10.1158/0008-5472.CAN-07-1960

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Cancer research

PubMed ID

18199542