The role of RHAMM in cancer: Exposing novel therapeutic vulnerabilities

Receptor for hyaluronic acid-mediated motility (RHAMM) is a cell surface receptor for hyaluronic acid that is critical for cell migration and a cell cycle protein involved in microtubule assembly and stability. These functions of RHAMM are required for cellular stress responses and cell cycle progression but are also exploited by tumor cells for malignant progression and metastasis. RHAMM is often overexpressed in tumors and is an independent adverse prognostic factor for a number of cancers such as breast and prostate. Interestingly, pharmacological or genetic inhibition of RHAMM in vitro and in vivo ablates tumor invasiveness and metastatic spread, implicating RHAMM as a potential therapeutic target to restrict tumor growth and improve patient survival. However, RHAMM's pro-tumor activity is dependent on its subcellular distribution, which complicates the design of RHAMM-directed therapies. An alternative approach is to identify downstream signaling pathways that mediate RHAMM-promoted tumor aggressiveness. Herein, we discuss the pro-tumoral roles of RHAMM and elucidate the corresponding regulators and signaling pathways mediating RHAMM downstream events, with a specific focus on strategies to target the RHAMM signaling network in cancer cells.

Automated summary

Receptor for hyaluronic acid-mediated motility (RHAMM) is a critical cell surface receptor involved in cell migration, cell cycle, and microtubule assembly. It is exploited by tumor cells to promote malignant progression and metastasis. Inhibition of RHAMM can suppress tumor invasiveness and metastatic spread and is considered a potential therapeutic target. However, the complexity of RHAMM's subcellular distribution complicates the design of targeted therapies. Identifying downstream signaling pathways of RHAMM may provide alternative strategies to control tumor aggressiveness.