Integrins emerge nowadays as crucial actors of
tumor aggressiveness and resistance to
therapies.
Integrin α5β1, the
fibronectin receptor, determines malignant properties of colon
carcinoma which is one of the most important causes of
cancer-related deaths in the world. Here we show that inhibition of α5
integrin subunit expression by
siRNA or α5β1
integrin function by specific antagonist affects the survival of HCT116
colon cancer cells. We also evidence that pharmacological reactivation of the
tumor suppressor p53 by
Nutlin-3a inhibits specifically the expression of the α5
integrin subunit both at the transcriptional and
protein level. Inversely repression of α5
integrin modulates p53 activity. A clear relationship between p53 activation by
Nutlin-3a, α5 repression and cell survival is shown. No such effects are obtained in cells lacking p53 or when another non-genotoxic activator of p53, RITA, is used. Our results emphasize the crucial role of α5β1
integrin in colon
tumors. Data also suggest that interfering with the
integrin α5β1 through the reactivation of p53 by
Nutlin-3a may be of valuable interest as a new therapeutic option for colon
tumors expressing high level of the
integrin and a wild type p53.