Integrin-Linked Kinase Inactives the Wnt Pathway through Connexin

Youping Yang, Hongxia Lin,

Abstract

One of the hallmarks of cancers is the silencing of tumor suppressor genes and certain signaling pathways. The Wnt pathway is activated in many types of cancers, leading to tumor progression and metastasis. Here we demonstrated that integrin-linked kinase (ILK) plays a critical role in the suppression of the Wnt pathway via decreasing Wnt3a-induced stabilization of β-catenin, which leaded to the block of the functional gap-junctional intercellular communications (GJIC). Inhibition of ILK in prostate cells resulted in the inactivation of the Wnt pathway components GSK3β and inactivation of Lef1 transcription with concomitant inducing of connexins, which forming channels between adjacent cells. In line with the above changes, over-expression of connexin 43 (Cx43) also inhibited the activity of Lef1 transcription factor induced by Wnt3a media and the transcription of target genes of Wnt signaling. Together, our data demonstrates a role for ILK as a regulator of Wnt pathway through Cx43 which is a negative feedback regulation of Wnt signaling and ILK may be a potential cancer therapeutic target.