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Cell Death Dis. 2015 May 7;6:e1740. doi: 10.1038/cddis.2015.92.

The synergistic interaction between the calcineurin B subunit and IFN-γ enhances macrophage antitumor activity.

Author information

1
1] Department of Biochemistry and Molecular Biology, Beijing Normal University, Gene Engineering and Biotechnology Beijing Key Laboratory, Beijing, PR China [2] Department of Biochemistry and Molecular Biology, Medical School, Southeast University, Nanjing, Jiangsu, PR China [3] Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
2
Department of Biochemistry and Molecular Biology, Beijing Normal University, Gene Engineering and Biotechnology Beijing Key Laboratory, Beijing, PR China.
3
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Macrophages are involved in tumor growth and progression. They infiltrate into tumors and cause inflammation, which creates a microenvironment favoring tumor growth and metastasis. However, certain stimuli may induce macrophages to act as tumor terminators. Here we report that the calcineurin B subunit (CnB) synergizes with IFN-γ to make macrophages highly cytotoxic to cancer cells. Furthermore, CnB and IFN-γ act synergistically to polarize mouse tumor-associated macrophages, as well as human monocyte-derived macrophages to an M1-like phenotype. This synergy is mediated by the crosstalk between CnB-engaged integrin αM-p38 MAPK signaling and IFN-γ-initiated p38/PKC-δ/Jak2 signaling. Interestingly, the signal transducer and activator of transcription 1 (STAT1) is a key factor that orchestrates the synergy of CnB and IFN-γ, and the phosphorylation status at Ser727 and Tyr701 of STAT1 is directly regulated by CnB and IFN-γ.

PMID:
25950470
PMCID:
PMC4669720
DOI:
10.1038/cddis.2015.92
[Indexed for MEDLINE]
Free PMC Article

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