SENP3 loss promotes M2 macrophage polarization and breast cancer progression.

ABSTRACT: Tumor-associated macrophages (TAM) play a crucial role in promoting cancer progression. Upon cytokine stimulation, TAM preferentially polarize to the anti-inflammatory and pro-tumor M2 subtype. The mechanism underlying such preferential polarization remains elusive. Here, we report that macrophage-specific deletion of the SUMO-specific protease Sentrin/SUMO-specific protease 3 promotes macrophage polarization towards M2 in bone marrow-derived macrophage (BMDM) induced by interleukin 4 (IL-4)/IL-13 and in an ex vivo model (murine Py8119 cell line), as well as in a mouse orthotopic tumor model. Notably, Sentrin/SUMO-specific protease 3 (SENP3) loss in macrophages accelerated breast cancer malignancy in ex vivo and in vivo models. Mechanistically, we identified Akt Serine/threonine kinase 1 (

SUBMITTER: Xiao M 

PROVIDER: S-EPMC8847990 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature