CD151 regulates HGF-stimulated morphogenesis of human breast cancer cells.
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.
Klosek
Sebastian K
SK
Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.
Nakashiro
Koh-ichi
K
Hara
Shingo
S
Goda
Hiroyuki
H
Hasegawa
Hitoshi
H
Hamakawa
Hiroyuki
H
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D055785:Gene Knockdown Techniques; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D039422:Integrin alpha3 / Q000378:metabolism; D039503:Integrin alpha6 / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D060185:Tetraspanin 24
D015703:Antigens, CD; C554715:CD151 protein, human; C066855:HGF protein, human; D039422:Integrin alpha3; D039503:Integrin alpha6; D034741:RNA, Small Interfering; D060185:Tetraspanin 24; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt