Uronic acid pathway metabolites regulate mesenchymal transition and invasiveness in lung adenocarcinoma.

Abstract

Metastatic transition results in the greatest morbidity and mortality in patients with cancer (1). Metastasis is a step-wise process that results in local extravasation and hematological dissemination of epithelial tumors (1). Local extravasation involves remodeling extracellular matrix (ECM) coupled with cellular invasion, a process promoted by epithelial mesenchymal transition (EMT). EMT is a complex cellular reprogramming event resulting in dissolution of mucosal tight junctions, loss of apical-basal polarity, reorganization of the cytoskeleton promoting motility and secretion of ECM-modifying proteins (2,3). In epithelial tumors, EMT is triggered by its local stromal microenvironment, including inflammatory cytokines, presence of hypoxia and secretion of epithelial growth factors. Understanding the factors controlling EMT in stem-ness, metastatic potential, chemotherapy resistance and how EMT can be modulated to affect cancer metastasis have been the focus of intense investigation.