RGS6 Inhibits the Proliferation, Migration, and Invasion of Breast Cancer Through the SMAD6-HMGA1 Signaling Pathway

Abstract The regulator of G protein signal 6 (RGS6) is a newly discovered tumor inhibitor that protects against the development of various types of cancer such as lung and bladder cancer. However, the mechanisms underlying these tumor-inhibition effects of RGS6 are not fully understood. In this study, we described the role of RGS6 in inhibiting the proliferation, migration, and invasion of breast cancer (BC) in vivo. Using bioinformatics and experimental tools, we found that RGS6 was generally downregulated in breast cancer tissues while a low expression of RGS6 was associated with poorer survival and prognosis of patients with breast cancer compared to those with normal breast tissues. The overexpression of RGS6 inhibited the migration and invasion of tumor cells by HMGA1. The results of rescue experiments showed that SMAD6 in the TGF-β signaling pathway plays a key role in this inhibitory effect of RGS6. Additionally, the ability of RGS6 to inhibit the expression of the HMGA1 gene depends on its ability to inhibit SMAD6. Based on these results, we identified a new function of RGS6 in regulating HMGA1-induced EMT and the proliferation, migration, and invasion of BC. The results suggested that RGS6 can act as an indicator of prognosis and might be a new target for treating breast cancer. This strategy can improve the outcomes of patients and transform therapeutic approaches.