Epithelial NAIPs protect against colonic tumorigenesis

The Journal of Experimental Medicine
Ramanjaneyulu AllamKendle M Maslowski

Abstract

NLR family apoptosis inhibitory proteins (NAIPs) belong to both the Nod-like receptor (NLR) and the inhibitor of apoptosis (IAP) families. NAIPs are known to form an inflammasome with NLRC4, but other in vivo functions remain unexplored. Using mice deficient for all NAIP paralogs (Naip1-6(Δ/Δ)), we show that NAIPs are key regulators of colorectal tumorigenesis. Naip1-6(Δ/Δ) mice developed increased colorectal tumors, in an epithelial-intrinsic manner, in a model of colitis-associated cancer. Increased tumorigenesis, however, was not driven by an exacerbated inflammatory response. Instead, Naip1-6(Δ/Δ) mice were protected from severe colitis and displayed increased antiapoptotic and proliferation-related gene expression. Naip1-6(Δ/Δ) mice also displayed increased tumorigenesis in an inflammation-independent model of colorectal cancer. Moreover, Naip1-6(Δ/Δ) mice, but not Nlrc4-null mice, displayed hyper-activation of STAT3 and failed to activate p53 18 h after carcinogen exposure. This suggests that NAIPs protect against tumor initiation in the colon by promoting the removal of carcinogen-elicited epithelium, likely in a NLRC4 inflammasome-independent manner. Collectively, we demonstrate a novel epithelial-intrinsic function of ...Continue Reading

References

Sep 1, 1993·Digestive Diseases and Sciences·S N MurthyD J Sedergran
Jan 6, 2000·Transgenic Research·B E ClausenI Förster
Jan 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·E DiezP Gros
Aug 25, 2000·Genome Research·M G EndrizziW F Dietrich
Sep 5, 2002·Nature Reviews. Molecular Cell Biology·David E Levy, J E Darnell
May 13, 2004·Cancer Immunology, Immunotherapy : CII·T EndoK Hirokawa
Jun 11, 2004·Nature·Sanjeev MariathasanVishva M Dixit
Jul 29, 2004·The Journal of Biological Chemistry·Jamshid DavoodiAlexander E MacKenzie
Sep 17, 2004·Nature·Jeremy SchmutzEdward M Rubin
Dec 13, 2005·The Journal of Biological Chemistry·Brendan P Eckelman, Guy S Salvesen
Oct 4, 2006·EMBO Reports·Brendan P EckelmanFiona L Scott
Apr 5, 2007·Nature Protocols·Stefan WirtzMarkus F Neurath
Dec 8, 2009·Gastroenterology·Monica MusteanuRobert Eferl
Feb 23, 2010·The International Journal of Biochemistry & Cell Biology·Jamshid DavoodiAlex Mackenzie
Apr 14, 2010·The Journal of Experimental Medicine·Irving C AllenJenny P-Y Ting
Apr 28, 2010·Gastroenterology·Janos TerzićMichael Karin
Jul 7, 2010·The Journal of Experimental Medicine·Petr BrozDenise M Monack
Dec 2, 2010·Proceedings of the National Academy of Sciences of the United States of America·Bo HuRichard A Flavell
May 6, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Grace Y ChenGabriel Núñez
Nov 19, 2011·Cancer Cell·Md Hasan ZakiThirumala-Devi Kanneganti
Aug 21, 2012·Nature·Jakob von MoltkeRussell E Vance
Oct 16, 2012·The American Journal of Pathology·Laurie A Shuman MossWilliam G Stetler-Stevenson
Oct 24, 2012·Proceedings of the National Academy of Sciences of the United States of America·Stefan K DrexlerAmir S Yazdi

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Citations

Mar 18, 2016·Cell and Tissue Research·B WonnenbergT Tschernig
Apr 6, 2016·The Journal of Experimental Medicine·Isabella RauchRussell E Vance
Jul 15, 2015·Trends in Immunology·Mikael E SellinWolf-Dietrich Hardt
Jun 12, 2016·Molecular Biology and Evolution·Stephanie A BryantJeramiah J Smith
Oct 28, 2016·Scientific Reports·Beichu GuoZihai Li
Apr 13, 2017·Mucosal Immunology·N ZmoraE Elinav
Apr 4, 2017·Cellular & Molecular Immunology·Ha Zhu, Xuetao Cao
Jul 8, 2016·Nature·Christoph A ThaissEran Elinav
Mar 7, 2019·Bioscience Reports·Fernando J VellosoRicardo G Correa
Jan 7, 2017·Scientific Reports·Francisco Abadía-MolinaAlex MacKenzie
May 21, 2019·Clinical and Experimental Immunology·K M Maslowski
Oct 6, 2017·Frontiers in Immunology·Andrea C Lei-LestonKevin J Maloy
Mar 8, 2019·Nature Reviews. Cancer·Rajendra Karki, Thirumala-Devi Kanneganti
Aug 17, 2020·International Journal of Molecular Sciences·Giulia PoliStefano Brancorsini
Sep 7, 2018·Nature Reviews. Gastroenterology & Hepatology·Si Ming Man
Oct 14, 2017·Immunological Reviews·Deepika Sharma, Thirumala-Devi Kanneganti
Nov 26, 2020·Journal of Molecular Histology·Julio Plaza-DíazFrancisco Abadía-Molina
Jan 18, 2017·Cancer Immunology Research·Rajendra KarkiThirumala-Devi Kanneganti
Nov 1, 2020·Current Opinion in Microbiology·Stefan A FattingerWolf-Dietrich Hardt
Jul 20, 2021·Frontiers in Immunology·Jiexia WenYimin Wang
Oct 11, 2021·Journal of Molecular Biology·Madeline J ChurchillIsabella Rauch
Dec 3, 2021·Biochemical Society Transactions·Lisa ScarfeKendle M Maslowski

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Methods Mentioned

BETA
PCR
flow cytometry
ELISA
biopsy
IEC
FACS

Software Mentioned

FlowJo
ImageJ

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