Major vault protein regulates tumor-associated macrophage polarization through interaction with signal transducer and activator of transcription 6

Chen Yu; Qingmei Zhu; Caijiao Ma; Chuanjin Luo; Longyu Nie; Huanhuan Cai; Qiming Wang; Fubing Wang; Hong Ren; Huan Yan; Ke Xu; Li Zhou; Caiyan Zhang; Guoping Lu; Zhibing Lu; Ying Zhu; Shi Liu

doi:10.3389/fimmu.2023.1289795

Major vault protein regulates tumor-associated macrophage polarization through interaction with signal transducer and activator of transcription 6

Front Immunol. 2024 Jan 9:14:1289795. doi: 10.3389/fimmu.2023.1289795. eCollection 2023.

Authors

Chen Yu¹, Qingmei Zhu¹, Caijiao Ma¹, Chuanjin Luo¹, Longyu Nie¹, Huanhuan Cai^{2

3}, Qiming Wang⁴, Fubing Wang⁵, Hong Ren⁶, Huan Yan¹, Ke Xu¹, Li Zhou¹, Caiyan Zhang⁶, Guoping Lu⁶, Zhibing Lu^{2

3}, Ying Zhu¹, Shi Liu^{1

2

4

5}

Affiliations

¹ State Key Laboratory of Virology, Modern Virology Research Center, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, Wuhan, China.
² Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China.
³ Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
⁴ College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan, Changsha, China.
⁵ Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China.
⁶ Shanghai Children's Medical Center, Affiliated Hospital to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Tumor-associated macrophages (TAMs) are critical in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). Major vault protein (MVP) mediates multidrug resistance, cell growth and development, and viral immunity. However, the relationship between MVP and TAMs polarization has not been clarified in HCC. We found that MVP significantly increased M2-TAMs infiltration levels in tumor tissues of HCC patients. MVP promoted HCC proliferation, metastasis, and invasion by regulating M2 polarization in vivo and in vitro. Mechanistically, MVP associated with signal transducer and activator of transcription 6 (STAT6) and enhanced STAT6 phosphorylation. STAT6 translocated from the cytosol to the nucleus and regulated M2 macrophage-associated gene transcription. These findings suggest that MVP modulates the macrophage M2 transcriptional program, revealing its potential role in the TAMs of TME.

Keywords: HCC; MVP; STAT6; TAMs; TME; polarization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular*
Humans
Liver Neoplasms*
STAT6 Transcription Factor* / metabolism
Tumor Microenvironment
Tumor-Associated Macrophages
Vault Ribonucleoprotein Particles* / metabolism

Substances

major vault protein
STAT6 Transcription Factor
Vault Ribonucleoprotein Particles
STAT6 protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Key Research and Development Program of China (2021YFC2701800, 2021YFC2701804), the National Natural Science Foundation of China (U22A20335), the Fundamental Research Funds for the Central Universities (2042022dx0003), the Science Fund for Distinguished Young Scholars of Hubei Province (2021CFA054), the Huxiang high-level talents gather engineering innovation and entrepreneurship talents in Hunan province (2021RC5006), the Fundamental Research Funds for the Central Universities (2042021kf023), the National Natural Science Foundation of China (81872262) and Deutsche For schungsgemeinschaft (Transregio TRR60).