E3 ligase FBXW7 restricts M2-like tumor-associated macrophage polarization by targeting c-Myc.

Abstract:

:FBXW7 functions as an E3 ubiquitin ligase to mediate oncoprotein degradation via the ubiquitin-proteasome system in cancer cells, effectively inhibiting the growth and survival of tumor cells. However, little is known about the functions of FBXW7 in macrophages and the tumor immune microenvironment. In this study, we find that FBXW7 suppresses M2-like tumor-associated macrophage (TAM) polarization to limit tumor progression. We identified a significant increase in the proportion of M2-like TAMs and aggravated tumor growth in mice with myeloid FBXW7 deficiency by subcutaneous inoculation with Lewis lung carcinoma cells (LLCs). When stimulated with LLCs supernatant in vitro, FBXW7-knockout macrophages displayed increased M2 macrophage polarization and enhanced ability of supporting cancer cells growth. In mechanism, we confirmed that FBXW7 inhibited M2-like TAM polarization by mediating c-Myc degradation via the ubiquitin-proteasome system. These findings highlight the role of FBXW7 in M2-like TAM polarization and provide new insights into the potential targets for cancer immunotherapies.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Zhong L,Zhang Y,Li M,Song Y,Liu D,Yang X,Yang D,Qu H,Lai L,Wang Q,Chen Z

doi

10.18632/aging.202293

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

24394-24423

issue

23

issn

1945-4589

pii

202293

journal_volume

12

pub_type

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