Implication of α2β1 integrin in anoikis of MCF-7 human breast carcinoma cells

Silencing of alpha 2 beta 1 integrin expression significantly promoted anchorage-dependent apoptosis (anoikis) and drastically reduced clonal activity of MCF-7 human breast carcinoma cells. Depletion of alpha 2 beta 1 enhanced the production of apoptotic protein p53 and of inhibitor of cyclin-dependent protein kinases, p27, while downregulating antiapoptotic protein Bcl-2 and multifunctional protein cMyc. Blocking the expression of alpha 2 beta 1 had no effect on activity of protein kinase Akt, but it sharply increased the kinase activity of Erk1/2. Pharmacological inhibition of Erk1/2 had a minor effect on anoikis of control cells, while it reduced anoikis of cells with downregulated alpha 2 beta 1 to the level of control cells. The data show for the first time that integrin alpha 2 beta 1 is implicated in the protection of tumor cells from anoikis through a mechanism based on the inhibition of protein kinase Erk.