title: Upregulation of sex-determining region Y-box 9 (SOX9) promotes cell proliferation and tumorigenicity in esophageal squamous cell carcinoma.
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.
authors.affiliation: Department of Thoracic Surgery, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen 510000, China.
authors.forename: Yingcai
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Anorectal Surgery, Shenzhen Second People's Hospital, Shenzhen 518035, China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Ning
authors.affiliation: Intensive Care Unit, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen 510000, China.
authors.forename: Huaisheng
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, China.
authors.forename: Ruiqing
authors.initials: R
authors.lastname: Shi
authors.affiliation: Department of Thoracic Surgery, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen 510000, China.
authors.forename: Shaolin
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Thoracic Surgery, Quanzhou First Hospital, the Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China.
authors.forename: Rongyu
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human
keywords: Akt; ESCC; SOX9; proliferation