Integrin α8β1 confers anoikis susceptibility to human intestinal epithelial crypt cells

We previously reported that integrin alpha 8 beta 1 is expressed in human intestinal epithelial crypt cells (HIECs) and represents one of the major RGD-binding integrins expressed by these cells. Moreover, the depletion of alpha 8 beta 1 affects vinculin, but not paxillin, localization at focal adhesion points. In the present study, we show that the integrin alpha 8 shRNA-mediated knockdown in HIECs leads to a decrease in anoikis susceptibility under cell suspension culture conditions, marked by a reduction in PARP cleavage and propidium iodide incorporation. Moreover, alpha 8 beta 1-depleted HIECs exhibited an illicitly sustained activation of Fak and PI3-K/Akt-1 under anoikis conditions, rendering them refractory to anoikis. To this effect, colon cancer cells exhibiting resistance to anoikis not only displayed a loss of alpha 8 beta 1 expression, but forced expression of alpha 8 beta 1 in these cells decreased their resistance to anoikis. Consequently, alpha 8 beta 1 is a prerequisite for the proper conduct of anoikis in normal HIECs, whereas its loss contributes to the illicit acquisition of anoikis resistance. (C) 2010 Elsevier Inc. All rights reserved.