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- Title
IRF5 suppresses metastasis through the regulation of tumor-derived extracellular vesicles and pre-metastatic niche formation.
- Authors
Roberts, Bailey K.; Li, Dan Iris; Somerville, Carter; Matta, Bharati; Jha, Vaishali; Steinke, Adison; Brune, Zarina; Blanc, Lionel; Soffer, Samuel Z.; Barnes, Betsy J.
- Abstract
Metastasis is driven by extensive cooperation between a tumor and its microenvironment, resulting in the adaptation of molecular mechanisms that evade the immune system and enable pre-metastatic niche (PMN) formation. Little is known of the tumor-intrinsic factors that regulate these mechanisms. Here we show that expression of the transcription factor interferon regulatory factor 5 (IRF5) in osteosarcoma (OS) and breast carcinoma (BC) clinically correlates with prolonged survival and decreased secretion of tumor-derived extracellular vesicles (t-dEVs). Conversely, loss of intra-tumoral IRF5 establishes a PMN that supports metastasis. Mechanistically, IRF5-positive tumor cells retain IRF5 transcripts within t-dEVs that contribute to altered composition, secretion, and trafficking of t-dEVs to sites of metastasis. Upon whole-body pre-conditioning with t-dEVs from IRF5-high or -low OS and BC cells, we found increased lung metastatic colonization that replicated findings from orthotopically implanted cancer cells. Collectively, our findings uncover a new role for IRF5 in cancer metastasis through its regulation of t-dEV programming of the PMN.
- Subjects
EXTRACELLULAR vesicles; INTERFERON regulatory factors; TRANSCRIPTION factors; METASTASIS; TUMOR microenvironment
- Publication
Scientific Reports, 2024, Vol 14, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-024-66168-w