Eukaryotic Translation Elongation Factor 1A Induces Anoikis by Triggering Cell Detachment

• Published in: The Journal of biological chemistry Vol. 287; no. 19; pp. 16037 - 16046
• Main 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.05.2012; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; Anoikis; Anoikis - drug effects; Anoikis - physiology; Apoptosis; Binding Sites; Cell Adhesion; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cell Detachment; Cell Line; Cell Line, Tumor; Cell Membrane - metabolism; Cell Survival - drug effects; Cell Survival - physiology; Culture Media, Serum-Free - pharmacology; Electrophoresis, Polyacrylamide Gel; Eukaryotic Initiation Factor-1 - genetics; Eukaryotic Initiation Factor-1 - metabolism; Eukaryotic Initiation Factor-1 - physiology; Extracellular Matrix - metabolism; Extracellular Matrix - physiology; Fibronectin; Fibronectins - metabolism; Fibronectins - physiology; Glycobiology and Extracellular Matrices; Humans; K562 Cells; Matrix Metalloproteinase (MMP); Mice; Microscopy, Confocal; Molecular Sequence Data; NIH 3T3 Cells; Peptide Elongation Factor 1 - genetics; Peptide Elongation Factor 1 - metabolism; Peptide Elongation Factor 1 - physiology; RNA Interference; Translation Elongation Factors; Cell Detachment; Translation Elongation Factors; Anoikis; Cell Adhesion; Matrix Metalloproteinase (MMP); Fibronectin; Apoptosis
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.308122

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. Background: Fibronectin harbors a cryptic antiadhesive site that is able to inactivate β-1 integrins. Results: Spontaneous anoikis of nontransformed fibroblasts was caused by exposure of this antiadhesive site and its recognition by membrane-resident eEF1A. Conclusion: eEF1A functions as a membrane receptor triggering cell detachment, resulting in anoikis. Significance: The results demonstrate a new function of eEF1A that contributes to cell regulation, including anoikis.