title: Recovery of anoikis in Src-transformed cells and human breast carcinoma cells by restoration of the SIRP α1/SHP-2 signaling system.
abstract: Src kinase dysregulation contributes to cancer progression but mechanistic understanding for this contribution remains incomplete. Signal regulatory protein α1 (SIRPα1) is a tumor suppressor that is constitutively suppressed in v-Src-transformed cells, where restoration of SIRPα1 expression inhibits anchorage-independent growth. In this study, we investigated the role of the protein tyrosine phosphatase-2 (SHP-2) in SIRPα1 activity. SHP-2 suppression resulted in a blockade of SIRPα1-mediated inhibition of anchorage-independent growth. Notably, we found that SIRPα1 did not act in v-Src-transformed cells by triggering cell growth arrest but by eliciting a suspension-selective apoptosis (anoikis), and that SHP-2 was required for this effect. Furthermore, we found that SHP-2 was crucial for recovery of stress fiber and focal contact formation by SIRPα1 in v-Src-transformed cells. Finally, we found that SIRPα1/SHP-2 signaling regulates anoikis in human breast carcinoma cells with activated c-Src. Taken together, our findings define SHP-2 as an essential component of tumor suppression and anoikis mediated by SIRPα1 in human breast carcinoma cells as well as in v-Src-transformed cells.
authors.affiliation: Department of Gastroenterology and Division of Cancer Biology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
authors.forename: Md Helal Uddin
authors.initials: MH
authors.lastname: Biswas
authors.forename: Hitoki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Satoko
authors.initials: S
authors.lastname: Ito
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hyodo
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Niwa
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
authors.forename: Michinari
authors.initials: M
authors.lastname: Hamaguchi
mesh_terms: D000818:Animals; D023102:Anoikis / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics* / Q000502:physiology; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014162:Transfection
chemical_list: D000943:Antigens, Differentiation; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11