Implication of integrin α5β1 in human breast carcinoma apoptosis and drug resistance

Doxorubicin-resistant MCF-7Dox line, which is a derivative of the drug-sensitive MCF-7 human breast carcinima line, differs from the latter by a strongly reduced expression of the α2β1 integrin and a highly increased expression of the α5β1 receptor. Silencing of this integrin in the MCF-7Dox cells by transfection with α5-specific siRNA markedly stimulated anoikis and increased sensitivity of the cells to doxorubicin. α5β1 silencing also leads to significant inhibition of the activity of kinases Akt and Erk2 in MCF-7Dox cells. Our results suggest that integrins α5β1-induced signals, controlling distinct aspects of cell behavior, are conducted through the common signal pathways.