IGDQ motogenic peptide gradient induces directional cell migration through integrin ( ?v)?3 activation in MDA-MB-231 metastatic breast cancer cells *

In the context of breast cancer metastasis study, we have shown in an in vitro model of cell migration that IGDQ-exposing (IsoLeuGly-Asp-Glutamine type I Fibronectin motif ) monolayers (SAMs) on gold sustain the adhesion of breast cancer MDA-MB-231 cells by triggering Focal Adhesion Kinase and integrin activation. Such tunable scaffolds are used to mimic the tumor extracellular environment, inducing and controlling cell migration. The observed migratory behavior induced by the IGDQ-bearing peptide gradient along the surface allows to separate cell subpopulations with a stationary or migratory phenotype. In this work, we knocked down the integrins alpha 5( beta 1) and ( alpha v) beta since they are already known to be implicated in cell migration. To this aim, a whole proteomic analysis was performed in beta 3 integrin (ITGB3) or alpha 5 integrin (ITGA5) knock-down MDA-MB-231 cells, in order to highlight the pathways implied in the integrin-dependent cell migration. Our results showed that i) ITGB3 depletion influenced ITGA5 mRNA expression, ii) ITGB3 and ITGA5 were both necessary for IGDQ-mediated directional single cell migration and iii) integrin ( alpha v) beta 3 was activated by IGDQ fibronectin type I motif. Finally, the proteomic analysis suggested that co-regulation of recycling transport of ITGB3 by ITGA5 is potentially necessary for directional

Automated summary

In the context of breast cancer metastasis study, the study investigated the regulation mechanism of cell migration and found that the IGDQ fibronectin motif activates integrin and influences cell migration. Integrins α5 and αv are related to cell migration, and they control cell migration by regulating the expression and function of ITGA5 and ITGB3.