SIPA1 enhances SMAD2/3 expression to maintain stem cell features in breast cancer cells

Stem Cell Research

Li Su¹  Xue Zhang²  Yiping Gong²  Nagahiro Minato³  Jueping Feng⁴  Rui Sun⁴  Qiongrong Chen⁵  Jun Weng⁶  Jing Xia⁶  Yangjin Zhu⁶  Die Hu⁶  Ning Wang⁶ 

[1] Department of Breast Surgery, Hubei Cancer Hospital, Wuhan 430079, China;Department of Breast Surgery, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, China;Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan;Department of Oncology, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430034, China;Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China;Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China;

关键词: Breast cancer;    Cancer stem cell;    SIPA1;    SMADs;    CD44;   

DOI  :  

来源: DOAJ

【 摘 要 】

SIPA1, a GTPase activating protein that negatively regulates Ras-related protein (Rap), is a potential modulator of tumor metastasis and recurrence. In this study, we first showed that SIPA1 facilitated the stemness features of breast cancer cells, such as of tumorsphere formation capability and the expression of stemness marker CD44. In addition, SIPA1 promoted the expression of four stemness-associated transcription factors through increasing the expression of SMAD2 and SMAD3 in vitro and in vivo. The stemness features were abolished by blocking the phosphorylation of SMAD3 with its specific inhibitor SIS3. Furthermore, SIPA1 decreased the breast cancer cell sensitivity to chemotherapy drugs. This effect was, however, competitively reversed by blocking the SMAD3 phosphorylation by SIS3 treatment in breast cancer cells. Taken together, SIPA1 promotes and sustains the stemness of breast cancer cells and their resistance to chemotherapy by increasing the expression of SMAD2 and SMAD3, and blocking SMAD3 phosphorylation could suppress the cancer cell stemness and increase the sensitivity to chemotherapy in breast cancer cells expressing a high level of SIPA1.

【 授权许可】

Unknown