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

Abstract

Background: Fibronectin harbors a cryptic antiadhesive site that is able to inactivate ␤-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.

Tenascin-C-derived Peptide TNIIIA2 Highly Enhances Cell Survival and Platelet-derived Growth Factor (PDGF)-dependent Cell Proliferation through Potentiated and Sustained Activation of Integrin α5β1

“…These results suggested that TNC stimulated cell proliferation through proteolytic exposure of the TNIIIA2-related cryptic proadhesive site of the TN-C molecule. We previously detected the secretion of an active form of MMP-2 from NIH3T3 cells (38). Moreover, the TN-C-induced stimulation of cell proliferation was inhibited by the function-blocking mAb directed to the integrin ␣5 subunit but not by mAbs directed to the ␣4 and ␣v subunits (Fig.…”

EEF1A1 (eukaryotic translation elongation factor 1 alpha 1)

“…Recent evidences show eEF1A to act as a membrane receptor for the cryptic anti-adhesive site of fibronectin, which contributes to cell regulation, including anoikis, through negative modulation of cell anchorage. Possibly, the membrane-resident eEF1A may interact with beta1-integrins inactivating their functions in cell adhesion (Itagaki et al, 2012). Down-regulation of eEF1A1 seems to be specific to senescence.…”

“…No other gene is present in the wasted deletion, and transgenic studies have shown that the EEF1A1 (eukaryotic translation elongation factor 1 alpha 1) Scaggiante B, Bosutti A Atlas Genet Cytogenet Oncol Haematol. 2015;19(4) phenotype is due to loss of eEF1A2 translation activity in muscle (Doig et al, 2013;Abbott et al, 2009). In neuronal cells, an eEF1A1 interaction with the yeast two-hybrid protein K (HYPK), highlights the involvement of HYPK in the regulation of cell growth, cell cycle, unfolded protein response and cell death.…”

“…Thus EEF1A1 (eukaryotic translation elongation factor 1 alpha 1) Scaggiante B, Bosutti A Atlas Genet Cytogenet Oncol Haematol. 2015;19(4) EEF1A1 down-regulation might be involved in the tumour cell progression toward the metastasis (Zhou et al, 2006).…”

“…eEF1A1 is up-regulated in human prostate cancer as resulted by iTRAQ-based analysis of serum samples derived from patients EEF1A1 (eukaryotic translation elongation factor 1 alpha 1) Scaggiante B, Bosutti A Atlas Genet Cytogenet Oncol Haematol. 2015;19(4) with prostatic disease and by immunohistochemistry of prostate cancer tissues with localized metastasis. Bone metastases represent the major risk in patients with prostate cancer progression.…”