TSSC3 represses self-renewal of osteosarcoma stem cells and Nanog expression by inhibiting the Src/Akt pathway

// Guang-Ning Yan 1 , Xue-Feng Tang 1 , Xian-Chao Zhang 2 , Ting He 3 , Yu-Sheng Huang 1 , Xi Zhang 1 , Gang Meng 1 , De-Yu Guo 2 , Yang-Fan Lv 1 and Qiao-Nan Guo 1 1 Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, PR China 2 Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China 3 Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China Correspondence to: Qiao-Nan Guo, email: qiaonan85@263.net , guoqn@tmmu.edu.cn Yang-Fan Lv, email: lovelvyangfan@163.con , 499058089@qq.com Keywords: TSSC3, Nanog, osteosarcoma, cancer stem cells, SRC Received: January 04, 2017      Accepted: June 10, 2017      Published: August 24, 2017 ABSTRACT Osteosarcoma is the most common type of bone cancer, and the second leading cause of cancer-related death in children and young adults. Osteosarcoma stem cells are essential for osteosarcoma initiation, metastasis, chemoresistance and recurrence. In the present study, we report that: 1) higher TSSC3 expression indicates a better prognosis for osteosarcoma patients, and; 2) overexpression of TSSC3 significantly decreases sphere-forming capacity, tumor initiation, stemness-related surface markers and Nanog expression in osteosarcoma cells. We also discovered that higher Nanog expression correlates to a worse prognosis for osteosarcoma patients, and overexpression of Nanog increases the stem-related phenotype in osteosarcoma cells. Knockdown of Nanog suppresses these phenotypes. Inhibition of Nanog expression and self-renewal of osteosarcoma cells by TSSC3 overexpression appears to be mediated through inactivation of the Src/Akt pathway. In the clinical setting, expression of TSSC3, p-Src and Nanog is associated with recurrence, metastasis and surgical intervention. Lower TSSC3 expression, higher Nanog expression or higher p-Src expression indicate a poor prognosis for osteosarcoma patients. Overall, our study demonstrates that TSSC3 inhibits the stem-like phenotype and Nanog expression by inactivation of the Src/Akt pathway; this emphasizes the importance of Nanog in osteosarcoma stem cells.