SCIENCE@home

mda-9/Syntenin Protein Positively Regulates the Activation of Akt Protein by Facilitating Integrin-linked Kinase Adaptor Function during Adhesion to Type I Collagen*

C. Hwangbo,Juhee Park,Jeong-Hyung Lee

Published 2011 in Journal of Biological Chemistry

ABSTRACT

Background: We investigated the role of mad-9/syntenin, a cancer metastasis inducer, in ILK adaptor function during adhesion to type I collagen. Results: mda-9/syntenin positively regulates the scaffold function of ILK. Conclusion: mda-9/syntenin regulates the activation of ILK signaling molecules by facilitating ILK adaptor function during adhesion to type I collagen. Significance: We describe a new mechanism of mda-9/syntenin for regulation of cancer metastasis. The integrin-linked kinase (ILK)-PINCH1-α-parvin (IPP) complex functions as a signaling platform for integrins that modulates various cellular processes. ILK functions as a central adaptor for the assembly of IPP complex. We report here that mda-9/syntenin, a positive regulator of cancer metastasis, regulates the activation of Akt (also known as protein kinase B) by facilitating ILK adaptor function during adhesion to type I collagen (COL-I) in human breast cancer cells. COL-I stimulation induced the phosphorylation and plasma membrane translocation of Akt. Inhibition of mda-9/syntenin or expression of mutant ILK (E359K) significantly blocked the translocation of both ILK and Akt to the plasma membrane. mda-9/syntenin associated with ILK, and this association was increased at the plasma membrane by COL-I stimulation. Knockdown of mda-9/syntenin impaired COL-I-induced association of ILK with Akt and plasma membrane targeting of ILK-Akt complex. These results demonstrated that mda-9/syntenin regulates the activation of Akt by controlling the plasma membrane targeting of Akt via a mechanism that facilitates the association of Akt with ILK at the plasma membrane during adhesion to COL-I. On a striking note, inhibition of mda-9/syntenin impaired COL-I-induced plasma membrane translocation of the IPP complex and assembly of integrin β1-IPP signaling complexes. Thus, our study defines the role of mda-9/syntenin in ILK adaptor function and describes a new mechanism of mda-9/syntenin for regulation of cell migration.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

CONCEPTS

REFERENCES

Showing 1-44 of 44 references · Page 1 of 1

CITED BY

Showing 1-27 of 27 citing papers · Page 1 of 1