The Autophagic Route of E-Cadherin and Cell Adhesion Molecules in Cancer Progression

Simple Summary A hallmark of carcinoma progression is the loss of epithelial integrity. In this context, the deregulation of adhesion molecules, such as E-cadherin, affects epithelial structures and associates with epithelial to mesenchymal transition (EMT). This, in turn, fosters cancer progression. Autophagy endows cancer cells with the ability to overcome intracellular and environmental stress stimuli, such as anoikis, nutrient deprivation, hypoxia, and drugs. Furthermore, it plays an important role in the degradation of cell adhesion proteins and in EMT. This review focuses on the interplay between the turnover of adhesion molecules, primarily E-cadherin, and autophagy in cancer progression. Cell-to-cell adhesion is a key element in epithelial tissue integrity and homeostasis during embryogenesis, response to damage, and differentiation. Loss of cell adhesion and gain of mesenchymal features, a phenomenon known as epithelial to mesenchymal transition (EMT), are essential steps in cancer progression. Interestingly, downregulation or degradation by endocytosis of epithelial adhesion molecules (e.g., E-cadherin) associates with EMT and promotes cell migration. Autophagy is a physiological intracellular degradation and recycling process. In cancer, it is thought to exert a tumor suppressive role in the early phases of cell transformation but, once cells have gained a fully transformed phenotype, autophagy may fuel malignant progression by promoting EMT and conferring drug resistance. In this review, we discuss the crosstalk between autophagy, EMT, and turnover of epithelial cell adhesion molecules, with particular attention to E-cadherin.