Abstract A36: Function of GPR56 in metastasis dormancy of melanoma

Abstract

Abstract Dormancy imposes significant challenges for cancer diagnosis and prognosis. We use pairs of metastatic melanoma cell lines that have different abilities to form metastases to investigate the molecular mechanisms of metastatic dormancy. We found that a novel receptor, GPR56, was down-regulated in highly metastatic melanoma cells compared with the poorly metastatic parental line. Re-expression of GPR56 in five different melanoma cell lines resulted in inhibition of metastasis formation in mouse lung. RNAseq analyses revealed that GPR56 might regulate the expression of genes involved in cellular homeostasis. Furthermore, our preliminary data show that GPR56 internalizes and degrades its ligand, TG2 from cell surface. TG2 is an ECM protein and functions to stabilize ECM and facilitate its signaling. The loss of TG2 resulting from GPR56 expression would disrupt ECM deposition and signaling in melanomas, ultimately leading to disturbance of cellular homeostasis of melanoma cells and their growth arrest. Taken together, we propose a model in which the novel receptor GPR56 sequesters metastatic melanomas at dormant states by down-regulating TG2 from cell surface and modulating cellular homeostasis. Citation Format: Nancy Corson, Michelle Warren, Lei Xu. Function of GPR56 in metastasis dormancy of melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A36.