OTUD5-mediated deubiquitination of YAP in macrophage promotes M2 phenotype polarization and favors triple-negative breast cancer progression

Macrophages, which are highly plastic, can be polarized to M1 or M2 subtypes according to the diverse signals in complex microenvironment. Studies have shown the activation of YAP, an oncogenic transcriptional co-activator, increased macrophage recruitment. However, its role in macrophage polarizati...

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Bibliographic Details
Published in:Cancer letters 2021-04, Vol.504, p.104-115
Main Authors: Zhang, Yujiao, Fan, Yizeng, Jing, Xin, Zhao, Lin, Liu, Tianjie, Wang, Lu, Zhang, Lifen, Gu, Shanzhi, Zhao, Xinhan, Teng, Yan
Format: Article
Language:English
Subjects:
Antibodies
Breast cancer
Cancer therapies
CCR2 protein
Cell growth
Chemotherapy
Estrogens
Experiments
Flow cytometry
Genotype & phenotype
Macrophage polarization
Macrophages
Medical prognosis
Metastases
Metastasis
Microenvironments
Monocyte chemoattractant protein 1
OTUD5
Phenotypes
Plasmids
Polarization
Survival analysis
TNBC
Transcription
Tumors
YAP
Yes-associated protein
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Summary:Macrophages, which are highly plastic, can be polarized to M1 or M2 subtypes according to the diverse signals in complex microenvironment. Studies have shown the activation of YAP, an oncogenic transcriptional co-activator, increased macrophage recruitment. However, its role in macrophage polarization remains to be elucidated, especially in triple-negative breast cancer (TNBC) progression. Here we found TNBC cells increased YAP expression in macrophages, which depended on OTUD5-mediated deubiquitination and stabilization of YAP, then the high expression of YAP polarized macrophage to the M2-like phenotype. Moreover, the elevation of YAP in M2-like macrophage promotes the pro-metastatic potential of TNBC cells via MCP-1/CCR2 pathway. We also observed high expression of YAP in M2 macrophage was negatively related to survival. Collectively, our finding suggested the therapeutic strategy that targets YAP+ M2 macrophage could be a novel option for TNBC treatment. •YAP is required for M2-like macrophage polarization.•OTUD5 deubiquitinates and stabilizes YAP.•YAP+M2 macrophage enhances the invasive potential of TNBC cells via MCP-1/CCR2.•YAP+M2 macrophage is positively related to the progression of TNBC.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2021.02.003