Integrin alpha8beta1 confers anoikis susceptibility to human intestinal epithelial crypt cells.
We previously reported that integrin alpha8beta1 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 alpha8beta1 affects vinculin, but not paxillin, localization at focal adhesion points. In the present study, we show that the integrin alpha8 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, alpha8beta1-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 alpha8beta1 expression, but forced expression of alpha8beta1 in these cells decreased their resistance to anoikis. Consequently, alpha8beta1 is a prerequisite for the proper conduct of anoikis in normal HIECs, whereas its loss contributes to the illicit acquisition of anoikis resistance.
Benoit
Yannick D
YD
CIHR Team on Digestive Epithelium, Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
Larrivée
Jean-François
JF
Groulx
Jean-François
JF
Stankova
Jana
J
Vachon
Pierre H
PH
Beaulieu
Jean-François
JF
D023102:Anoikis; D002478:Cells, Cultured; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D016023:Integrins; C094866:integrin alpha8beta1; D019869:Phosphatidylinositol 3-Kinases; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt