Integrin β5 contributes to the tumorigenic potential of breast cancer cells through the Src-FAK and MEK-ERK signaling pathways

摘要: Cancer progression, response to therapy and metastasis depend on tumor microenvironment. Integrins are cell-adhesion receptors that mediate interactions of cells with extracellular matrix. The αv-β-family integrins contributes tumorigenesis, cancer stem cell biology. Thus, understanding the function specific in is critical for development therapeutic approaches targeting integrins. study investigated role integrin β5 breast carcinomas by depleting using RNA interference reexpression β5. Depletion triple-negative carcinoma markedly reduced take, growth angiogenesis, whereas rescued this phenotype. Reduction angiogenesis associated lower expression vascular endothelial factor-A β5-depleted tumors. Tumor deficient have migration proliferative capacities. Biochemical assays revealed mediates Src-focal adhesion kinase MEK-extracellular signal-regulated signaling events operate independently, inhibition these pathways phenocopies deficiency. Breast express high levels β5, β3 limited stromal compartments β6 lost metastatic cells. Together, findings show a tumorigenic potential especially attractive carcinomas, which refractory most current therapies.