Modulation of EGF‐R signaling by desmoglein 2 in pancreatic cancer cells

Abstract

Desmogleins are cell adhesion molecules located both in desmosomes and extradesmosomal regions in the membrane with well‐established roles for intercellular adhesion and signaling. We have previously shown that loss of the most widespread desmoglein, Dsg2, increases malignant behavior and induces a non‐epithelial phenotype through dysregulation of Erk signaling in pancreatic cancer cell lines. Here, we further explored the interdependence of Dsg2 and EGFR/Erk signaling by using Dsg2 knockouts of the pancreatic cancer cell line AsPC‐1. Dsg2 knockout clones showed reduced cell adhesion, enhanced migration and augmented invasion in extracellular matrix. Dsg2 interacted with EGFR as demonstrated in immunoprecipitation experiments. However, upon serum depletion, the increased migratory capacity of Dsg2 knockouts was abrogated and not restored upon EGF treatment. This indicates that increased migration in response to Dsg2 loss is agonist‐dependent but independent of EGF. Furthermore, inhibition of EGFR tyrosin kinase activity using erlotinib was significantly less effective in reducing migration of knockouts compared to wildtype controls. In line with this, erlotinib treatment reduced ERK activity in wildtype controls but not in Dsg2 knockout cells and only partially reverted the non‐epithelial phenotype in response to Dsg2 loss. These data indicate that Dsg2 modulates the activity of EGFR signaling in an agonist‐dependent manner.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.