PRMT6 promotes lung tumor progression via the alternate activation of tumor-associated macrophages

Sreedevi Avasarala, Pei Ying Wu, Samia Q. Khan, Su Yanlin, Michelle Van Scoyk, Jianqiang Bao, Alessandra Di Lorenzo, Odile David, Mark T. Bedford, Vineet Gupta, Robert A. Winn, Rama Kamesh Bikkavilli

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Increased expression of protein arginine methyl transferase 6 (PRMT6) correlates with worse prognosis in lung cancer cases. To interrogate the in vivo functions of PRMT6 in lung cancer, we developed a tamoxifen-inducible lung-targeted PRMT6 gain-offunction mouse model, which mimics PRMT6 amplification events in human lung tumors. Lung-targeted overexpression of PRMT6 accelerated cell proliferation de novo and potentiated chemical carcinogen (urethane)-induced lung tumor growth. To explore the molecular mechanism/s by which PRMT6 promotes lung tumor growth, we used proteomics-based approaches and identified interleukin-enhancer binding protein 2 (ILF2) as a novel PRMT6-associated protein. Furthermore, by using a series of in vitro gain-of-function and loss-of-function experiments, we defined a new role for the PRMT6-ILF2 signaling axis in alternate activation of tumor-associated macrophages (TAM). Interestingly, we have also identified macrophage migration inhibitory factor, which has recently been shown to regulate alternate activation of TAMs, as an important downstream target of PRMT6-ILF2 signaling. Collectively, our findings reveal a previously unidentified noncatalytic role for PRMT6 in potentiating lung tumor progression via the alternate activation of TAMs.

Original languageEnglish (US)
Pages (from-to)166-178
Number of pages13
JournalMolecular Cancer Research
Volume18
Issue number1
DOIs
StatePublished - 2020
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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