Recovery of anoikis in Src-transformed cells and human breast carcinoma cells by restoration of the SIRPα1/SHP-2 signaling system

Kazuo Hara, Takeshi Senga, Md Helal Uddin Biswas, Hitoki Hasegawa, Satoko Ito, Toshinori Hyodo, Yoshiki Hirooka, Yasumasa Niwa, Hidemi Goto, Michinari Hamaguchi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1229-1234
Number of pages6
JournalCancer Research
Volume71
Issue number4
DOIs
Publication statusPublished - 15-02-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Recovery of anoikis in Src-transformed cells and human breast carcinoma cells by restoration of the SIRPα1/SHP-2 signaling system'. Together they form a unique fingerprint.

Cite this