Integrin α8β1 confers anoikis susceptibility to human intestinal epithelial crypt cells

We previously reported that integrin α8β1 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 α8β1 affects vinculin, but not paxillin, localization at focal adhesion points. In the present study, we show that the integrin α8 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, α8β1-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 α8β1 expression, but forced expression of α8β1 in these cells decreased their resistance to anoikis. Consequently, α8β1 is a prerequisite for the proper conduct of anoikis in normal HIECs, whereas its loss contributes to the illicit acquisition of anoikis resistance.

Research highlights► Integrin α8β1 is expressed at significant levels in normal intestinal crypt cells. ► Integrin α8β1 deficiency confers anoikis resistance to human intestinal crypt cells. ► Lack of integrin α8β1 leads to constitutive FAK/PI3-K/Akt pathway activation. ► Integrin α8β1 is absent from anoikis-resistant colorectal cancer cells. ► Forced expression of α8β1 confers anoikis susceptibility to colorectal cancer cells.