Upregulation of sex-determining region Y-box 9 (SOX9) promotes cell proliferation and tumorigenicity in esophageal squamous cell carcinoma.
Upregulation of sex-determining region Y-box 9 (SOX9) promotes cell proliferation and tumorigenicity in esophageal squamous cell carcinoma.
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DOI：
10.18632/oncotarget.5160
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发表时间：
2015-10-13
期刊：
影响因子：
--
通讯作者：
Zhou H
中科院分区：
文献类型：
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作者：
Hong Y;Chen W;Du X;Ning H;Chen H;Shi R;Lin S;Xu R;Zhu J;Wu S;Zhou H
性别决定区Y-box 9（SOX 9）是一种重要的转录因子，在许多生物学和病理学过程中发挥重要作用。然而，SOX 9表达的临床意义和生物学作用尚未在人食管鳞状细胞癌（ESCC）中得到表征。在此，我们发现SOX 9在mRNA和蛋白水平上在ESCC细胞系和ESCC组织中显著上调，并且SOX 9表达与肿瘤临床分期、T分类、N分类、M分类、病理分化和较短的总生存期显著相关。在体外和体内，SOX 9过表达显著诱导ESCC细胞的增殖和致瘤性，但SOX 9敲低则抑制ESCC细胞的增殖和致瘤性。此外，我们证明，上调SOX 9增加磷酸化Akt的表达，细胞周期蛋白依赖性激酶（CDK）调节剂细胞周期蛋白D1，磷酸化叉头盒O（FOXO）1，磷酸化FOXO 3，但SOX 9下调降低其表达，而CDK抑制剂p21 Cip 1和p27 Kip 1的水平在SOX 9转导的细胞中减弱。总之，我们的研究结果表明，SOX 9在促进食管鳞癌的增殖和肿瘤发生中起着重要作用，并可能代表该疾病的一种新的预后标志物。
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.