Chemokine/GPCR Signaling-Mediated EMT in Cancer Metastasis

Metastasis, the chief cause of cancer-related deaths, is associated with epithelial-mesenchymal transition (EMT). In the tumor microenvironment, EMT can be triggered by chemokine/G-protein-coupled receptor (GPCR) signaling, which is closely associated with tumor progression. However, the functional links between chemokine/GPCR signaling-mediated EMT and metastasis remain unclear. Herein, we summarized the mechanisms of chemokine/GPCR signaling-mediated EMT with an insight into facilitating metastasis and clarified the role of chemokine in the local invasion, intravasation, circulation, extravasation, and colonization, respectively. Moreover, several potential pathways that might contribute to EMT based on the latest studies on GPCR signaling were proposed, including signaling mediated by G protein, beta-arrestin, intracellular, dimerization activation, and transactivation. However, there is still limited evidence to support the EMT programme functional contribution to metastasis, which keeps a key question still open whether we should target EMT programme of cancer cells. Answers to that question might help develop an anticancer strategy or guide new directions for anticancer metastasis therapy.