title: GFI1 downregulation promotes inflammation-linked metastasis of colorectal cancer.
abstract: Inflammation is frequently associated with initiation, progression, and metastasis of colorectal cancer (CRC). Here, we unveil a CRC-specific metastatic programme that is triggered via the transcriptional repressor, GFI1. Using data from a large cohort of clinical samples including inflammatory bowel disease and CRC, and a cellular model of CRC progression mediated by cross-talk between the cancer cell and the inflammatory microenvironment, we identified GFI1 as a gating regulator responsible for a constitutively activated signalling circuit that renders CRC cells competent for metastatic spread. Further analysis of mouse models with metastatic CRC and human clinical specimens reinforced the influence of GFI1 downregulation in promoting CRC metastatic spread. The novel role of GFI1 is uncovered for the first time in a human solid tumour such as CRC. Our results imply that GFI1 is a potential therapeutic target for interfering with inflammation-induced CRC progression and spread.
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin 150081, China.|Immunity & Infection Key laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Xing
authors.affiliation: Department of Bioinformatics, College of Bioinformatics, Harbin Medical University, Harbin 150081, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin 150081, China.|Immunity & Infection Key laboratory of Heilongjiang Province, Harbin 150081, China.|Center of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin 150081, China.|Immunity & Infection Key laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin 150081, China.|Immunity & Infection Key laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Xiangchuan
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin 150081, China.|Immunity & Infection Key laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
authors.forename: Elsa S
authors.initials: ES
authors.lastname: Lopez
authors.affiliation: Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Wong
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin 150081, China.|Immunity & Infection Key laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Ju
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin 150081, China.|Immunity & Infection Key laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Linlu
authors.initials: L
authors.lastname: Tian
authors.affiliation: Immunity & Infection Key laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin 150081, China.|Immunity & Infection Key laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Xu
authors.affiliation: Center of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Sheng Dian
authors.initials: SD
authors.lastname: Wang
authors.affiliation: Department of Bioinformatics, College of Bioinformatics, Harbin Medical University, Harbin 150081, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin 150081, China.|Immunity & Infection Key laboratory of Heilongjiang Province, Harbin 150081, China.|College of basic medicine, Shanghai University Of Medicine & Health Sciences, Shanghai 201318, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Ren
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C498275:GFI1 protein, human; C545644:PTGER2 protein, human; D034741:RNA, Small Interfering; D058307:Receptors, Prostaglandin E, EP2 Subtype; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt