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.
journal_name
Proc Natl Acad Sci U S Aauthors
Suarez-Lopez L,Sriram G,Kong YW,Morandell S,Merrick KA,Hernandez Y,Haigis KM,Yaffe MBdoi
10.1073/pnas.1722020115subject
Has Abstractpub_date
2018-05-01 00:00:00pages
E4236-E4244issue
18eissn
0027-8424issn
1091-6490pii
1722020115journal_volume
115pub_type
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