Coordinate integrin and c-Met signaling regulate Wnt gene expression during epithelial morphogenesis

Abstract

Integrin receptors for the extracellular matrix and receptor tyrosine kinase growth factor receptors represent two of the major families of receptors that transduce into cells information about the surrounding environment. Wnt proteins are a major family of signaling molecules that regulate morphogenetic events. There is presently little understanding of how the expression of Wnt genes themselves is regulated. In this study, we demonstrate that α3β1 integrin, a major laminin receptor involved in the development of the kidney, and c-Met, the receptor for hepatocyte growth factor, signal coordinately to regulate the expression of Wnt7b in the mouse. Wnt signals in turn appear to regulate epithelial cell survival in the papilla of the developing kidney, allowing for the elongation of epithelial tubules to form a mature papilla. Together, these results demonstrate how signals from integrins and growth factor receptors can be integrated to regulate the expression of an important family of signaling molecules so as to regulate morphogenetic events.

α6β1 and α7β1 Integrins Are Required in Schwann Cells to Sort Axons

“…␣6 integrin "floxed" ( F ) mice will be described (A. De Arcangelis et al, manuscript in preparation); ␣7 integrin knock-out and ␣3 integrin floxed mice have been described Liu et al, 2009). ␣6 integrin constitutive heterozygous null mice were the progeny of animals obtained by crossing ␣6 integrin F/ϩ animals and CMV-Cre animal.…”

“…Mice of either sex were used. Genotyping of mutant mice was performed by PCR on tail genomic DNA, as described previously (Feltri et al, 1999Liu et al, 2009;Germain et al, 2010).…”

“…5B), suggesting lack of compensation, but not excluding redundancy. To investigate a possible role for ␣3 integrin in axonal sorting, we thus produced ␣3 conditional null mice (␣3cKO) by crossing ␣3 integrin floxed (Liu et al, 2009) (Fig. 5A).…”

Targeting MET in Cancer: Obstacles and Potentials

“…MET pathway also interacts with WNT signaling. WNT-β-catenin stimulate MET transcription in colon cancer cell lines, and MET and integrin α3β1 signaling in turn regulate the transcription of WNT7B [38]. Furthermore, HGF stimulate LRP5/6 phosphorylation and promotes WNT signaling in the kidney [39].…”

Le récepteur Met fête ses 30 ans

“…L'association entre Met et l'intégrine α6β4 est ainsi importante pour l'invasion cellulaire [25]. Met peut aussi interagir avec l'intégrine α3β1, favorisant le recrutement de GAB1 et de la PI3K, et le contrôle de la voie Wnt [26]. L'interaction de Met avec l'isoforme CD44v6 favorise quant à elle la phosphorylation de Met par son ligand, mais aussi une activation plus efficace de la voie Ras-ERK (extracellular signal-regulated kinase), via l'association de la région intracellulaire de CD44v6 avec les protéines ERM (ezrine, radixine et moésine) [27].…”