RHAMM inhibits cell migration via the AKT/GSK3β/Snail axis in luminal A subtype breast cancer

Abstract

Breast cancer is one of the most common types of cancer in women. Although the mortality rate of breast cancer has fallen over the past 10 years, effective treatments that reduce the occurrence of breast cancer metastasis remain lacking. In this study, we explored the role of receptor for hyaluronan mediated motility (RHAMM) and the associated signaling pathway in cell migration in luminal A breast cancer. We first examined RHAMM expression levels using human breast tissue microarray and patient breast tissues. We then studied the role of RHAMM in migration in luminal A breast cancer using loss-of-function and gain-of-function strategies in in vitro models and confirmed these findings in an in vivo model. Finally, we investigated signaling molecules that play a role in cell migration using western blot. Our results demonstrated the following: (a) RHAMM shows high expression levels in malignant breast tissue, (b) RHAMM shows low expression levels in luminal A breast cancer compared to other subtypes of breast cancer, (c) RHAMM inhibits cell migration in luminal A breast cancer, and (d) RHAMM inhibits cell migration via the AKT/GSK3β/Snail axis in luminal A breast cancer. This study demonstrates a novel role of RHAMM in cell migration in luminal A breast cancer and suggests that therapeutic strategies involving RHAMM should be considered for various subtypes of breast cancer.