CD151 regulates HGF-stimulated morphogenesis of human breast cancer cells.

Abstract

We previously demonstrated that CD151 forms a functional complex with c-Met and integrin alpha3/alpha6 in human salivary gland cancer cells. In the current study, we investigated the involvement of CD151, c-Met, and integrin alpha3/alpha6 in the cellular morphogenesis of human breast cancer cells. Knockdown of CD151, integrin alpha3, or integrin alpha6 expression abolished branching morphogenesis. Decreased c-Met expression in these cells led to the formation of rudimentary networks and prevented their conversion. Furthermore, hepatocyte growth factor (HGF) promoted cellular morphogenesis by accelerating network reorganization. Immunoprecipitation revealed a specific association between CD151 and c-Met. The involvement of CD151 and integrin alpha3/alpha6 in HGF-dependent signaling was confirmed by the decreased Akt phosphorylation in cells lacking CD151, integrin alpha3, or integrin alpha6. Hence, the regulation of CD151 expression might contribute to changes in HGF/c-Met signaling and thereby modulate the phenotypic characteristics of cancer cells.

• Authors: Sebastian K Klosek, Koh-ichi Nakashiro, Shingo Hara, Hiroyuki Goda, Hitoshi Hasegawa, Hiroyuki Hamakawa
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 379 Issue 4 Pg. 1097-100 (Feb 20 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19159612 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• CD151 protein, human
• HGF protein, human
• Integrin alpha3
• Integrin alpha6
• RNA, Small Interfering
• Tetraspanin 24
• Hepatocyte Growth Factor
• Proto-Oncogene Proteins c-met
• Proto-Oncogene Proteins c-akt

Topics

• Antigens, CD (genetics, metabolism)
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Transformation, Neoplastic (genetics, metabolism, pathology)
• Female
• Gene Knockdown Techniques
• Hepatocyte Growth Factor (metabolism, pharmacology)
• Humans
• Integrin alpha3 (metabolism)
• Integrin alpha6 (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-met (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Tetraspanin 24