Identification of the interplay between SOX9 and S100P in the metastasis and invasion of colon carcinoma
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Zhiyong Shen1,*, Haijun Deng1,*, Yuan Fang2, Xianjun Zhu1, Geng-tai Ye1, Li Yan1, Hao Liu1, Guoxin Li1
1Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
2Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
*These authors have contributed equally to this work
Guoxin Li, e-mail: [email protected]
Hao Liu, e-mail: [email protected]
Keywords: SOX9, S100P, transcriptional regulation, metastasis and invasion, epithelial-mesenchymal transition
Received: December 12, 2014 Accepted: April 30, 2015 Published: May 13, 2015
Elevated expression of S100P has been detected in several tumor types and suggested to be responsible for tumor metastasis and invasion, but the upstream regulatory mechanisms promoting S100P overexpression are largely unknown. Here, we report that SOX9 was predicted and verified as a transcription factor of S100P. SOX9 and S100P were both overexpressed in colon cancer. SOX9 bound to and activated the S100P promoter. Knockdown of SOX9 expression down-regulated S100P expression, resulting in reduced invasiveness and metastasis of colon cancer cells by inhibiting the activation of receptor for advanced glycation end products (RAGE)/ERK signaling and epithelial-mesenchymal transition (EMT). Further, decreased expression of SOX9 dramatically inhibited the tumor growth and peritoneal metastasis in nude mice. More importantly, S100P was found to be critical for SOX9-mediated metastasis and invasion in colon cancer. Knockdown of S100P in SOX9-overexpressing colon cancer cells dramatically suppressed metastasis and invasion both in vitro and in mice. We also detected SOX9 and S100P expression in a tissue microarray with 90 colon cancer cases to provide their clinical relevance. There was a strong correlation between SOX9 and S100P expression in colon carcinomas. In conclusion, our results suggest that SOX9 promotes tumor metastasis and invasion through regulation of S100P expression.
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