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.
Highlights
Fibronectin harbors a cryptic antiadhesive site that is able to inactivate -1 integrins
These results demonstrate that Eukaryotic elongation factor 1A (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
When NIH3T3 cells adhering to the fibronectin were cultured under serum-starved conditions, the number of viable cells decreased in a time-dependent manner, which was in parallel with an increase in the detached cell number (Fig. 1A)
Summary
Fibronectin harbors a cryptic antiadhesive site that is able to inactivate -1 integrins. 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. 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. Besides the canonical role as a cytosolic factor in polypeptide chain elongation during protein translation, our results provide evidence of a new function of eEF1A as a membrane receptor for triggering cell detachment from the ECM, which contributes to cell regulation, including anoikis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
