α7 helix region of αI domain is crucial for integrin binding to endoplasmic reticulum chaperone gp96: a potential therapeutic target for cancer metastasis.

Titleα7 helix region of αI domain is crucial for integrin binding to endoplasmic reticulum chaperone gp96: a potential therapeutic target for cancer metastasis.
Publication TypeJournal Article
Year of Publication2013
AuthorsHong F, Liu B, Chiosis G, Gewirth DT, Li Z
JournalThe Journal of biological chemistry
Volume288
Issue25
Pagination18243-8
Date Published2013 Jun 21
Abstract

Integrins play important roles in regulating a diverse array of cellular functions crucial to the initiation, progression, and metastasis of tumors. Previous studies have shown that a majority of integrins are folded by the endoplasmic reticulum chaperone gp96. Here, we demonstrate that the dimerization of integrin αL and β2 is highly dependent on gp96. The αI domain (AID), a ligand binding domain shared by seven integrin α-subunits, is a critical region for integrin binding to gp96. Deletion of AID significantly reduced the interaction between integrin αL and gp96. Overexpression of AID intracellularly decreased surface expression of gp96 clients (integrins and Toll-like receptors) and cancer cell invasion. The α7 helix region is crucial for AID binding to gp96. A cell-permeable α7 helix peptide competitively inhibited the interaction between gp96 and integrins and blocked cell invasion. Thus, targeting the binding site of α7 helix of AID on gp96 is potentially a new strategy for treatment of cancer metastasis.

DOI10.1155/2013/405284
Alternate JournalJ. Biol. Chem.