title: SOX10, a novel HMG-box-containing tumor suppressor, inhibits growth and metastasis of digestive cancers by suppressing the Wnt/β-catenin pathway.
abstract: SOX10 was identified as a methylated gene in our previous cancer methylome study. Here we further analyzed its epigenetic inactivation, biological functions and related cell signaling in digestive cancers (colorectal, gastric and esophageal cancers) in detail. SOX10 expression was decreased in multiple digestive cancer cell lines as well as primary tumors due to its promoter methylation. Pharmacologic or genetic demethylation reversed SOX10 silencing. Ectopic expression of SOX10 in SOX10-deficient cancer cells inhibits their proliferation, tumorigenicity, and metastatic potentials in vitro and in vivo. SOX10 also suppressed the epithelial to mesenchymal transition (EMT) and stemness properties of digestive tumor cells. Mechanistically, SOX10 competes with TCF4 to bind β-catenin and transrepresses its downstream target genes via its own DNA-binding property. SOX10 mutations that disrupt the SOX10-β-catenin interaction partially prevented tumor suppression. SOX10is thus a commonly inactivated tumor suppressor that antagonizes Wnt/β-catenin signaling in cancer cells from different digestive tissues.
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai, China. PLA General Hospital Cancer Center Key Laboratory, Medical School of Chinese PLA, Beijing, China. Department of Pharmacy, Liao Cheng University, Shandong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tong
authors.affiliation: Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai, China. PLA General Hospital Cancer Center Key Laboratory, Medical School of Chinese PLA, Beijing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Heng
authors.affiliation: Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Su
authors.affiliation: Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Rong
authors.initials: R
authors.lastname: Rong
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Hu
authors.affiliation: PLA General Hospital Cancer Center Key Laboratory, Medical School of Chinese PLA, Beijing, China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Liu
authors.affiliation: PLA General Hospital Cancer Center Key Laboratory, Medical School of Chinese PLA, Beijing, China.
authors.forename: Baoqing
authors.initials: B
authors.lastname: Jia
authors.affiliation: 150 hospital of Chinese PLA, Luoyang, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai, China. Department of Pharmacy, Liao Cheng University, Shandong, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Kou
authors.affiliation: Department of Pharmacy, Liao Cheng University, Shandong, China. State Key Laboratory of Antibody Medicine & Targeting Therapy and Shanghai Key Laboratory of Cell Engineering & Antibody, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Pharmacy, Liao Cheng University, Shandong, China.
authors.forename: Shangjing
authors.initials: S
authors.lastname: Guo
authors.affiliation: PLA General Hospital Cancer Center Key Laboratory, Medical School of Chinese PLA, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: PLA General Hospital Cancer Center Key Laboratory, Medical School of Chinese PLA, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Qian
authors.initials: Q
authors.lastname: Tao
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai, China. PLA General Hospital Cancer Center Key Laboratory, Medical School of Chinese PLA, Beijing, China. Department of Pharmacy, Liao Cheng University, Shandong, China. State Key Laboratory of Antibody Medicine & Targeting Therapy and Shanghai Key Laboratory of Cell Engineering & Antibody, Shanghai, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D058750:Epithelial-Mesenchymal Transition; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin