title: Alterations in the microbiota drive interleukin-17C production from intestinal epithelial cells to promote tumorigenesis.
abstract: Although the microbiota has been shown to drive production of interleukin-17A (IL-17A) from T helper 17 cells to promote cell proliferation and tumor growth in colorectal cancer, the molecular mechanisms for microbiota-mediated regulation of tumorigenesis are largely unknown. Here, we found that the innate-like cytokine IL-17C was upregulated in human colorectal cancers and in mouse intestinal tumor models. Alterations in the microbiota drove IL-17C upregulation specifically in intestinal epithelial cells (IECs) through Toll-like receptor (TLR)-MyD88-dependent signaling during intestinal tumorigenesis. Microbiota-driven IL-17C induced Bcl-2 and Bcl-xL expression in IECs in an autocrine manner to promote cell survival and tumorigenesis in both chemically induced and spontaneous intestinal tumor models. Thus, IL-17C promotes cancer development by increasing IEC survival, and the microbiota can mediate cancer pathogenesis through regulation of IL-17C.
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Song
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Hanchao
authors.initials: H
authors.lastname: Gao
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yikun
authors.initials: Y
authors.lastname: Yao
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yao
authors.affiliation: The Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Guangxun
authors.initials: G
authors.lastname: Meng
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Rheumatology, Shanghai Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200001, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Research Institute for Biomedical Sciences, Tokyo University of Science, Yamazaki 2669, Noda-shi, Chiba 278-0022, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Rheumatology, Shanghai Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200001, China. Electronic address: ycqian@sibs.ac.cn.
authors.forename: Youcun
authors.initials: Y
authors.lastname: Qian
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D063646:Carcinogenesis / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000276:immunology* / Q000382:microbiology; D004195:Disease Models, Animal; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053594:Myeloid Differentiation Factor 88; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein