title: RIG-like Helicase Regulation of Chitinase 3-like 1 Axis and Pulmonary Metastasis.
abstract: Chi3l1 is induced by a variety of cancers where it portends a poor prognosis and plays a key role in the generation of metastasis. However, the mechanisms that Chi3l1 uses to mediate these responses and the pathways that control Chi3l1-induced tumor responses are poorly understood. We characterized the mechanisms that Chi3l1 uses to foster tumor progression and the ability of the RIG-like helicase (RLH) innate immune response to control Chi3l1 elaboration and pulmonary metastasis. Here we demonstrate that RLH activation inhibits tumor induction of Chi3l1 and the expression of receptor IL-13Rα2 and pulmonary metastasis while restoring NK cell accumulation and activation, augmenting the expression of IFN-α/β, chemerin and its receptor ChemR23, p-cofilin, LIMK2 and PTEN and inhibiting BRAF and NLRX1 in a MAVS-dependent manner. These studies demonstrate that Chi3l1 is a multifaceted immune stimulator of tumor progression and metastasis whose elaboration and tissue effects are abrogated by RLH innate immune responses.
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, Providence, R.I. 02912, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Ma
authors.affiliation: Yale University School of Medicine, Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, 300 Cedar Street (TAC S441), New Haven, CT 06520, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Herzog
authors.affiliation: Yale University School of Medicine, Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, 300 Cedar Street (TAC S441), New Haven, CT 06520, USA.
authors.forename: Meagan
authors.initials: M
authors.lastname: Moore
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, Providence, R.I. 02912, USA.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, Providence, R.I. 02912, USA.
authors.forename: Sung Hun
authors.initials: SH
authors.lastname: Na
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, Providence, R.I. 02912, USA.
authors.forename: Chun Geun
authors.initials: CG
authors.lastname: Lee
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, Providence, R.I. 02912, USA.|Division of Medical and Biological Sciences, Warren Alpert Medical School, Brown University, Providence, R.I. 02912, USA.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D000071451:Chitinase-3-Like Protein 1 / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D007113:Immunity, Innate; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary*; D008546:Melanoma, Experimental / Q000276:immunology / Q000556:secondary*; D008822:Mice, Transgenic; D011070:Poly I-C / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D000071451:Chitinase-3-Like Protein 1; D053663:Interleukin-13 Receptor alpha2 Subunit; D004265:DNA Helicases; D011070:Poly I-C