SRC-1 Promotes Colorectal Cancer Cell Proliferation,Migration And Invasion Via Hedgehog Signaling Pathway

Steroid receptor coactivator 1(SRC-1)is a member of Steroid receptor coactivator family.SRC-1 not only interacts with steroid receptors such as androgen receptor(AR)and estrogen receptor(ER),but also coactivates many other transcription factors,such as β-catenin,NF-κB,HNF4,HIF1,E2F1 and p53.SRC-1 has been shown to play an important role in the progression of breast and prostate cancer.However,its role in colorectal cancer progression remains unknown.In this study,we found that SRC-1 was overexpressed in colorectal cancer tissues and cell lines.Hence,we propose that SRC-1 play an important role in the progression of colorectal cancer.The results show that downregulation of SRC-1 decreased CRC cell proliferation and colony formation and impaired xenograft tumor growth.We also found that downregulation of SRC-1 decreased the CRC cell migration and invasion.In addition,SRC-1 could directly interacting with Gli2 that is the core transcription factor of Hedgehog signaling pathway and enhanced the transcriptional activity of Gli2 in a dose-dependent manner.And TCGA database analysis results showed that the high expression of SRC-1 was positively correlated with the low survival rate of colorectal cancer patients.In summary,our results demonstrate that SRC-1 promotes the proliferation,migration and invasion of CRC cells via Hedgehog signaling.Through the study of molecular mechanism of SRC-1 involved in the process of colorectal cancer,it is helpful to find the potential therapeutical target for colorectal cancer.