title: Blockade of MK2 is protective in inflammation-associated colorectal cancer development.
abstract: Chronic inflammation is a risk factor for colorectal cancer. The MAPK-activated protein kinase 2 (MK2) pathway controls multiple cellular processes including p38-dependent inflammation. This is the first study to investigate the role of MK2 in development of colitis-associated colon cancer (CAC). Herein, we demonstrate that MK2(-/-) mice are highly resistant to neoplasm development when exposed to AOM/DSS, while wild type (WT) C57BL/6 develop multiple neoplasms with the same treatment. MK2-specific cytokines IL-1, IL-6 and TNF-α were substantially decreased in AOM/DSS treated MK2(-/-) mouse colon tissues compared with WT mice, which coincided with a marked decrease in macrophage influx. Restoring MK2-competent macrophages by injecting WT bone marrow derived macrophages into MK2(-/-) mice led to partial restoration of inflammatory cytokine production with AOM/DSS treatment; however, macrophages were not sufficient to induce neoplasm development. These results indicate that MK2 functions as an inflammatory regulator to promote colonic neoplasm development and may be a potential target for CAC.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM.
authors.forename: Anita L
authors.initials: AL
authors.lastname: Ray
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM.
authors.forename: Eliseo F
authors.initials: EF
authors.lastname: Castillo
authors.affiliation: Department of Surgery, University of New Mexico, Albuquerque, NM.
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Morris
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Nofchissey
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM.
authors.forename: Lea L
authors.initials: LL
authors.lastname: Weston
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM.
authors.forename: Von G
authors.initials: VG
authors.lastname: Samedi
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Hanson
authors.affiliation: Department of Biochemistry, Hannover Medical University, Hannover, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gaestel
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Pinchuk
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Beswick
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007249:Inflammation / Q000150:complications*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2
keywords: Colorectal Cancer; IL-1; IL-6; MK2; TNF-α; macrophages