Recovery of anoikis in Src-transformed cells and human breast carcinoma cells by restoration of the SIRP α1/SHP-2 signaling system
| Autor: | Takeshi Senga, Satoko Ito, Toshinori Hyodo, Yasumasa Niwa, Kazuo Hara, Michinari Hamaguchi, Md. Helal Uddin Biswas, Hidemi Goto, Hitoki Hasegawa, Yoshiki Hirooka |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Stress fiber Proto-Oncogene Proteins pp60(c-src) Breast Neoplasms Protein Tyrosine Phosphatase Non-Receptor Type 11 Biology Transfection medicine Animals Humans Anoikis Tyrosine Receptors Immunologic Cells Cultured Regulation of gene expression Cell growth Carcinoma Cancer medicine.disease Antigens Differentiation Cell biology Rats Gene Expression Regulation Neoplastic Cell Transformation Neoplastic Oncology Apoptosis Female Proto-oncogene tyrosine-protein kinase Src Signal Transduction |
| Zdroj: | Cancer research. 71(4) |
| ISSN: | 1538-7445 |
| Popis: | 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. Cancer Res; 71(4); 1229–34. ©2010 AACR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|