Work

Systemic Propagation of STING Signalling via Generation of Large Extracellular Vesicles

Year: 2026

Type: article

Abstract: Large extracellular vesicles (EVs) derived from tumour cells play important roles in tumour formation and progression. However, it remains unclear why malignant cells produce these EVs and how they act in vivo. We employ a well-characterized Drosophila tumour model and demonstrate that large EV biogenesis from malignant cells is an evolutionarily conserved process. Our study uncovers an essential role for the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which mediates the innate immune response to cytosolic DNA, in driving large EV biogenesis and inducing a systemic immune response to tumours. STING engages a signalling axis comprising JNK and FAK-independent of TANK-binding kinase 1 (TBK1) and inhibitor of nuclear factor κB kinase (IKKβ)-to drive large EV biogenesis in both Drosophila and human malignant cells. Transplantation of large EVs from Drosophila tumours to wild type larvae is sufficient to recapitulate the systemic immune response to tumours by activating STING signalling in macrophage-like cells. Thus, our study establishes a novel animal model for studying large EVs derived from malignant cells and provides insights into how STING signalling propagates from tumour cells to the immune system via large EV biogenesis, inducing a systemic immune response to tumours.

Source: Journal of Extracellular Vesicles

DOI: 10.1002/jev2.70289

Authors: Jiae Lee, Annabel Vernon, Hyung Joon Park, Young V. Kwon

Institutions: University of Washington, California State University, Long Beach

Language: English

Topic: Extracellular vesicles in disease

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,410