Label-free quantitative proteomics of extracellular vesicles from BT549 cells following 3-day reversine treatment Label-free quantitative proteomics of extracellular vesicles from BT549 cells following 3-day reversine treatment

ABSTRACT: Chromosomal instability promotes cell migration and invasion via EFEMP1 secretion into extracellular vesicles Triple-negative breast cancer (TNBC) is characterised by high rates of chromosomal instability (CIN) and rewired intercellular communication driven by both soluble factors and extracellular vesicles (EVs). To assess how CIN might affect EV-mediated signalling in TNBC, we studied the EV landscape of TNBC cell lines with induced CIN. We find that CIN leads to increased secretion of EVs and that these EVs promote cell migration of recipient cells. EVs are enriched for extracellular matrix (ECM) proteins, including EFEMP1. Indeed, modulation of EFEMP1 levels in EVs significantly alters migration behaviour of EV-treated cells. We show that EFEMP1 expression is regulated by STAT1, and that EVs from STAT1-deficient cells no longer promote migration, which can be rescued by overexpression of EFEMP1 in STAT1-null cells. Xenografting TNBC cells with EFEMP1 enriched cells promotes migration in zebrafish embryos, suggesting that EFEMP1 expression is a factor that promotes metastasis. Together, our results identify a CIN-associated EV program in TNBC and highlight EFEMP1 as a potential therapeutic target to impair EV-driven tumour cell migration.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Breast Cancer

SUBMITTER: Justina Clarinda Wolters  

LAB HEAD: JC Wolters

PROVIDER: PXD073786 | Pride | 2026-03-10

REPOSITORIES: Pride