title: CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell growth through inducing G1 arrest.
abstract: Cytokines are soluble proteins that exert their functions by binding specific receptors. Many cytokines play essential roles in carcinogenesis and have been developed for the treatment of cancer. In this study, we identified a novel potential cytokine using immunogenomics designated colon-derived SUSD2 binding factor (CSBF), also known as chromosome 10 open reading frame 99 (C10orf99). CSBF/C10orf99 is a classical secreted protein with predicted molecular mass of 6.5 kDa, and a functional ligand of Sushi Domain Containing 2 (SUSD2). CSBF/C10orf99 has the highest expression level in colon tissue. Both CSBF/C10orf99 and SUSD2 are down-regulated in colon cancer tissues and cell lines with different regulation mechanisms. CSBF/C10orf99 interacts with SUSD2 to inhibit colon cancer cell growth and induce G1 cell cycle arrest by down-regulating cyclin D and cyclin-dependent kinase 6 (CDK6). CSBF/C10orf99 displays a bell-shaped activity curve with the optimal effect at ~10 ng/ml. Its growth inhibitory effects can be blocked by sSUSD2-Fc soluble protein. Our results suggest that CSBF/C10orf99 is a novel potential cytokine with tumor suppressor functions.
authors.affiliation: Department of Immunology, Center for Human Disease Genomics, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Immunology, Center for Human Disease Genomics, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: 1] Department of Immunology, Center for Human Disease Genomics, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China [2] Central Laboratory, Peking University School of Stomatology, Beijing, China.
authors.forename: Heyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Center for Human Disease Genomics, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Baocai
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Immunology, Center for Human Disease Genomics, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Mo
authors.affiliation: Department of Immunology, Center for Human Disease Genomics, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China [2] Department of Surgery, Peking University Cancer Hospital &Institute, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China [2] Department of Surgery, Peking University Cancer Hospital &Institute, Beijing, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Cheng
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China [2] Department of Surgery, Peking University Cancer Hospital &Institute, Beijing, China.
authors.forename: Lianhai
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China [2] Department of Surgery, Peking University Cancer Hospital &Institute, Beijing, China.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Immunology, Center for Human Disease Genomics, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Pingzhang
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Immunology, Center for Human Disease Genomics, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D011485:Protein Binding
chemical_list: D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; C000597433:GPR15LG protein, human; C582626:SUSD2 protein, human