Oncotarget

Research Papers:

Upregulation of sex-determining region Y-box 9 (SOX9) promotes cell proliferation and tumorigenicity in esophageal squamous cell carcinoma

Yingcai Hong, Wen Chen, Xiaojun Du, Huiwen Ning, Huaisheng Chen, Ruiqing Shi, Shaolin Lin, Rongyu Xu, Jinrong Zhu, Shu Wu and Haiyu Zhou _

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Oncotarget. 2015; 6:31241-31254. https://doi.org/10.18632/oncotarget.5160

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Abstract

Yingcai Hong1, Wen Chen2, Xiaojun Du3, Huiwen Ning4, Huaisheng Chen5, Ruiqing Shi3, Shaolin Lin1, Rongyu Xu6, Jinrong Zhu7, Shu Wu8, Haiyu Zhou3

1Department of Thoracic Surgery, Shenzhen People’s Hospital, the Second Clinical Medical College of Jinan University, Shenzhen 510000, China

2Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China

3Department of Thoracic Surgery, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, China

4Department of Anorectal Surgery, Shenzhen Second People’s Hospital, Shenzhen 518035, China

5Intensive Care Unit, Shenzhen People’s Hospital, the Second Clinical Medical College of Jinan University, Shenzhen 510000, China

6Department of Thoracic Surgery, Quanzhou First Hospital, the Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China

7Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China

8State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, China

Correspondence to:

Haiyu Zhou, e-mail: haiyu_zhou@126.com

Keywords: SOX9, ESCC, proliferation, Akt

Received: May 04, 2015     Accepted: August 24, 2015     Published: September 04, 2015

ABSTRACT

Sex-determining region Y-box 9 (SOX9), a vital transcription factor, play important roles in numerous biological and pathological processes. However, the clinical significance and biological role of SOX9 expression has not been characterized in human esophageal squamous cell cancer (ESCC). Herein, we found that SOX9 was markedly upregulated, at both mRNA and protein level, in ESCC cell lines and ESCC tissues and that SOX9 expression was significantly correlated with tumor clinical stage, T classification, N classification, M classification, pathological differentiation, and shorter overall survival. The proliferation and tumorigenicity of ESCC cells were dramatically induced by SOX9 overexpression but were inhibited by SOX9 knockdown both in vitro and in vivo. Moreover, we demonstrated that upregulation of SOX9 increased the expression of phosphorylated Akt, the cyclin-dependent kinase (CDK) regulator cyclin D1, phosphorylated forkhead box O (FOXO)1, and phosphorylated FOXO3, but SOX9 downregulation decreased their expression, whereas the levels of the CDK inhibitors p21Cip1 and p27Kip1 were attenuated in SOX9-transduced cells. Taken together, our results suggest that SOX9 plays an important role in promoting the proliferation and tumorigenesis of ESCC and may represent a novel prognostic marker for the disease.


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