title: Integrin-linked kinase regulates migration and proliferation of human intestinal cells under a fibronectin-dependent mechanism.
abstract: Integrin-linked kinase (ILK) plays a role in integrin signaling-mediated extracellular matrix (ECM)-cell interactions and also acts as a scaffold protein in functional focal adhesion points. In the present study, we investigated the expression and roles of ILK in human intestinal epithelial cells (IECs) in vivo and in vitro. Herein, we report that ILK and its scaffold-function interacting partners, PINCH-1, alpha-parvin, and beta-parvin, are expressed according to a decreasing gradient from the bottom of the crypt (proliferative/undifferentiated) compartment to the tip of the villus (non-proliferative/differentiated) compartment, closely following the expression pattern of the ECM/basement membrane component fibronectin. The siRNA knockdown of ILK in human IECs caused a loss of PINCH-1, alpha-parvin, and beta-parvin expression, along with a significant decrease in cell proliferation via a loss of cyclin D1 and an increase in p27 and hypophosphorylated pRb expression levels. ILK knockdown severely affected cell spreading, migration, and restitution abilities, which were shown to be directly related to a decrease in fibronectin deposition. All ILK knockdown-induced defects were rescued with exogenously deposited fibronectin. Altogether, our results indicate that ILK performs crucial roles in the control of human intestinal cell and crypt-villus axis homeostasis-especially with regard to basement membrane fibronectin deposition-as well as cell proliferation, spreading, and migration.
authors.affiliation: CIHR Team on the Digestive Epithelium, Département d'Anatomie et de Biologie Cellulaire, Université de Sherbrooke, Sherbrooke, Québec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Gagné
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Groulx
authors.forename: Yannick D
authors.initials: YD
authors.lastname: Benoit
authors.forename: Nuria
authors.initials: N
authors.lastname: Basora
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Herring
authors.forename: Pierre H
authors.initials: PH
authors.lastname: Vachon
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Beaulieu
mesh_terms: D000185:Actinin / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D018938:Caco-2 Cells; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D004268:DNA-Binding Proteins / Q000378:metabolism; D020895:Enterocytes / Q000201:enzymology*; D005353:Fibronectins / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D013997:Time Factors; D014161:Transduction, Genetic; D014162:Transfection; D000099200:Scaffold Protein ILK; D000096985:Calponins
chemical_list: D000185:Actinin; D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D005353:Fibronectins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C088088:LIMS1 protein, human; C486590:PARVA protein, human; D000096985:Calponins; C486591:PARVB protein, human