Research Paper Volume 12, Issue 23 pp 24394—24423
E3 ligase FBXW7 restricts M2-like tumor-associated macrophage polarization by targeting c-Myc
- 1 Department of Pulmonology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China
- 2 Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
- 3 Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China
- 4 Department of Orthopedic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China
Received: February 5, 2020 Accepted: September 24, 2020 Published: December 1, 2020
https://doi.org/10.18632/aging.202293How to Cite
Copyright: © 2020 Zhong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.