Eukaryotic translation elongation factor 1A induces anoikis by triggering cell detachment |
| |
Authors: | Itagaki Keisuke Naito Toshihiko Iwakiri Ryota Haga Makoto Miura Shougo Saito Yohei Owaki Toshiyuki Kamiya Sadahiro Iyoda Takuya Yajima Hirofumi Iwashita Shintaro Ejiri Shin-ichiro Fukai Fumio |
| |
Institution: | Department of Molecular Pathophysiology, Tokyo University of Science, Chiba 278-8510, Japan. |
| |
Abstract: | Anoikis, apoptosis because of loss of cell anchorage, is crucial for tissue homeostasis. Fibronectin not only provides a scaffold for cell anchorage but also harbors a cryptic antiadhesive site capable of inducing β1-integrin inactivation. In this study, this cryptic antiadhesive site is implicated in spontaneous induction of anoikis. Nontransformed fibroblasts (NIH3T3) adhering to a fibronectin substratum underwent anoikis during serum starvation culture. This anoikis was caused by proteolytic exposure of the cryptic antiadhesive site in fibronectin by matrix metalloproteinase. Eukaryotic elongation factor 1A (eEF1A) was identified as a membrane receptor for the exposed antiadhesive site. Serum starvation raised the membrane residence of eEF1A, and siRNA-based disruption of this increase rendered cells anoikis-resistant. By contrast, cells became more susceptible to anoikis in parallel with increased membrane residence of eEF1A by enforced expression. These results demonstrate that eEF1A acts as a membrane receptor for the cryptic antiadhesive site of fibronectin, which contributes to cell regulation, including anoikis, through negative regulation of cell anchorage. |
| |
Keywords: | Apoptosis Cell Adhesion Fibronectin Matrix Metalloproteinase (MMP) Translation Elongation Factors Anoikis Cell Detachment |
本文献已被 PubMed 等数据库收录! |
|