Modulation of integrin expression regulates expression of cell-cycle modulators known to induce G1 arrest. A. Western blots show the expression of cyclin E, cdk2, p27, pRb, chk1, cdc25A, and E2F1 in 4T1 control, 4T1 GFP, 4T1 α5 overexpressing, and 4T1 α6 knocked-down cells. B: Our current model showing the mechanism of integrin modulation in breast cancer progression. This model shows overexpression of integrin α5 or reduced expression of α6 causes upregulation of chk1. This, in turn, causes downregulation of cdk2/cyclin E to reduce phosphorylation of retinoblastoma protein. This integrin modulation enhances the expression of E2F, which may stimulate chk1 expression, which regulates cdc25a function, in a feedback loop mechanism.