TSSC3 represses self-renewal of osteosarcoma stem cells and Nanog expression by inhibiting the Src/Akt pathway
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Guang-Ning Yan1, Xue-Feng Tang1, Xian-Chao Zhang2, Ting He3, Yu-Sheng Huang1, Xi Zhang1, Gang Meng1, De-Yu Guo2, Yang-Fan Lv1 and Qiao-Nan Guo1
1Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, PR China
2Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China
3Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China
Keywords: TSSC3, Nanog, osteosarcoma, cancer stem cells, SRC
Received: January 04, 2017 Accepted: June 10, 2017 Published: August 24, 2017
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.
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