OncoTargets and Therapy (Apr 2018)
Combination of SIRT1 and Src overexpression suggests poor prognosis in luminal breast cancer
Abstract
Jie Tan,1,* Yuyin Liu,2,* Yusufu Maimaiti,3 Changwen Wang,1 Yu Yan,1 Jing Zhou,1 Shengnan Ruan,1 Tao Huang1 1Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 2Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 3Department of General Surgery, Research Institute of Minimally Invasive, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China *These authors contributed equally to this work Objectives: 1) Analyze the correlation of SIRT1 and Src with human breast cancer (BC) prognosis; 2) explore the roles of SIRT1 and Src in BC cell proliferation, tumor invasion, and metastasis; and 3) analyze the correlation and interaction between SIRT1 and Src. Materials and methods: 1) Tissue microarray was used to analyze the expression of SIRT1 and Src in human BC tissues and the correlation between protein expression and cancer prognosis; 2) CCK8 assay was used to determine the influence of SIRT1 and Src inhibitors on BC cell proliferation; 3) Transwell migration assay and wound healing assay were used to determine the effect of SIRT1 and Src inhibitors on BC cell migration and invasion; and 4) Western blotting was used to analyze the correlation and interaction between SIRT1 and Src. Results: 1) Combination of SIRT1 and/or Src positivity is a prognosis factor in BC, especially in luminal type; 2) MCF-7 cell proliferation is suppressed by SIRT1 inhibitor Ex527, and cell migration and invasion were inhibited by Src inhibitor bosutinib; 3) combined with Ex527, bosutinib has a significantly increased effect on MCF-7 cell migration suppression; and 4) there is a positive association between SIRT1 and Src both in BC tissues and in MCF-7 cells. Conclusion: 1) SIRT1 and Src overexpression are both correlated with poor prognosis in human BC; 2) SIRT1 + Src (SIRT1 and/or Src positivity) is a fine prognosis model for luminal-type BC; 3) SIRT1 is a copromotor of Src in BC migration and invasion, but not in cell proliferation; and 4) our results suggest a potential interaction or a common regulation pathway between SIRT1 and Src expression and activity. Keywords: breast cancer, SIRT1, Src, tissue microarray, estrogen receptor, cell migration
