IGPR-1 interacts with MIA to regulate melanoma cell migration and invasion
Embargo Date
2020-02-20
OA Version
Citation
Abstract
Melanoma represents one of the most aggressive and deadliest form of skin cancer. Melanoma inhibitory activity (MIA) also called cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a small secreted protein with a single Src Homology 3 (SH3) domain-like fold with N- and C-terminal extensions. MIA interacts with extracellular matrix proteins (ECM), such as fibronectin, laminin, tenascin, ECM receptors and integrins. It is proposed that MIA by interacting with ECM or integrins inhibits cell-ECM adhesion leads to increased melanoma cell migration and tumor invasion. However, the experimental data to support this proposed function of MIA remains poorly understood. We have identified immunoglobulin-containing and proline-rich receptor-1 (IGPR-1) as a novel binding partner for MIA. The main objectives of this project were to investigate IGPR-1 expression in human melanoma cell lines and primary tumors and explore the biological importance of IGPR-1/MIA axis in melanoma cell function. Our findings revealed that IGPR-1 expression is downregulated in melanoma cell lines. However, different levels of IGPR-1 expression have been observed. Moreover, IGPR-1 expression was significantly downregulated in human primary melanoma tumors. We demonstrate that co-expression of IGPR-1with MIA promotes cell survival and increase cell-cell adhesion. Taken together, our data suggests that IGPR-1/MIA pathway could regulate melanoma cell invasion and metastasis. We propose a novel cytosolic signaling function for MIA in melanoma cells.