MK2 contributes to tumor progression by promoting M2 macrophage polarization and tumor angiogenesis
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Author(s)
Haigis, Kevin M.
Suarez Lopez, Lucia
Kong, Yi Wen
Sriram, Ganapathy
Morandell, Sandra M.
Merrick, Karl Andrew
Hernandez, Yuliana I
Yaffe, Michael B
Date Issued
April 2018
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Citation
Suarez-Lopez, Lucia et al. “MK2 Contributes to Tumor Progression by Promoting M2 Macrophage Polarization and Tumor Angiogenesis.” Proceedings of the National Academy of Sciences (April 16, 2018): 201722020. © 2018 National Academy of Sciences
Version
Final published version
Abstract
Chronic inflammation is a major risk factor for colorectal cancer. The p38/MAPKAP Kinase 2 (MK2) kinase axis controls the synthesis of proinflammatory cytokines that mediate both chronic inflammation and tumor progression. Blockade of this pathway has been previously reported to suppress inflammation and to prevent colorectal tumorigenesis in a mouse model of inflammation-driven colorectal cancer, by mechanisms that are still unclear. Here, using whole-animal and tissue-specific MK2 KO mice, we show that MK2 activity in the myeloid compartment promotes tumor progression by supporting tumor neoangiogenesis in vivo. Mechanistically, we demonstrate that MK2 promotes polarization of tumor-associated macrophages into protumorigenic, proangiogenic M2-like macrophages. We further confirmed our results in human cell lines, where MK2 chemical inhibition in macrophages impairs M2 polarization and M2 macrophage-induced angiogenesis. Together, this study provides a molecular and cellular mechanism for the protumorigenic function of MK2. Keywords: MK2, macrophage polarization, tumor angiogenesis, inflammation, colon cancer
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
http://dx.doi.org/10.1073/PNAS.1722020115
