Title: Sonic Hedgehog stimulates migration of MCF-7 breast cancer cells through Rac1

Authors: Tian Shen1,2, Bo’ang Han1,3, Yan Leng4, Sen Yan1, Junfeng Shi5, Shen Yue1,3, Steven Y Cheng1,3

Institutions: 1 Jiangsu Key Laboratory of Xenotransplanation, Department of Medical Genetics, Nanjing Medical University, Nanjing, Jiangsu 211166, China; 2 Department of Pathology and Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China; 3 Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China; 4 Department of Pathology, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, China; 5 Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China.

Abstract: As one of the most common tumors in women, breast cancer has drawn considerable interest from investigators and clinicians in recent years. Despite early diagnosis and best therapeutic regimens available, the prognosis of malignant or metastatic breast cancer patients is still not optimistic. Hedgehog signaling, a classical pathway indispensable to embryonic development, participates in the growth of a variety of tumors. In the present study, the effect of Sonic Hedgehog (Shh) on breast cancer cells was investigated. We identified that Shh signal stimulated the migration of MCF-7 breast cancer cells. Smo and Gli1 were involved in Shh-stimulated migration of MCF-7 cells. Activating Smo and Gli1 induced cell migration, which was blocked by their specific antagonists. The effect of Shh signaling on MCF-7 cells was independent of Wnt5a, Dvl2 and Rab35, but directly dependent on Rac1. In conclusion, our study suggested that Shh promotes breast cancer cell migration via Rac1 independently of the non-canonical Wnt signaling pathway, which may represent a rational molecular target for combination medication in breast cancer.

Keywords: Shh, Rac1, breast cancer, MCF-7, migration

Full Text:

J Biomed Res published on 05 December, 2018, https://doi.org/10.7555/JBR.32.20180100