Abstract C32: The function of GPR56 in metastasis formation of melanoma

Abstract

Abstract Disseminated cancer cells often persist in tissues for a long period before being manifested as clinically detectable metastases. This metastasis dormancy imposes a main threat for cancer patients, especially after their first line of cancer treatment. Little is known as to how this dormancy is maintained and what triggers its awakening, but tumor microenvironment is thought to play a decisive role. We discovered that a member of newly described family of adhesion G protein-coupled receptors (GPCRs), GPR56, inhibits metastasis formation of melanoma cell lines and sequesters them at a dormant state in lung. GPR56 binds to TG2, a component in extracellular matrix (ECM) that could also function as a cross linking enzyme. It is significantly up-regulated in human melanoma metastases relative to the primary tumors and its expression promotes metastasis formation of melanoma cells in the experimental metastasis model. The down-regulation of TG2 by GPR56 may abolish the pro-metastasis function of TG2 in melanoma cells via destabilizing ECM and contribute to their sequestration at the dormant state. Furthermore, RNAseq analyses suggest that GPR56 may regulate the expression of factors involved in cellular homeostasis. It is thus possible that GPR56 maintains metastasis dormancy in melanoma by down-regulating TG2 in ECM and perturbing cellular homeostasis. Citation Format: Nancy Corson, Liquan Yang, Lei Xu. The function of GPR56 in metastasis formation of melanoma. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C32.