What question did this study set out to answer?

The study aims to identify how specific oncogenes and tumor suppressor genes affect extracellular vesicle (EV) secretion in colorectal cancer cells.

March 4, 2026Open Access

Functional siRNA Screen Links Ras/MAPK and Wnt Pathway to EV Secretion in HCT-116 Colorectal Cancer Cells

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Loss-of-function screen identifies gene impacts on EV secretion in colorectal cancer cells, suggesting key signaling pathways are involved.

The study aims to identify how specific oncogenes and tumor suppressor genes affect extracellular vesicle (EV) secretion in colorectal cancer cells.
Conducted siRNA-based loss-of-function screen targeting 30 (proto-)oncogenes and tumor suppressor genes.
Isolated EVs using sequential ultracentrifugation at different gravitational forces (P14 and P100 fractions).
Characterized EVs through nanoparticle tracking analysis, marker expression analysis, and total protein quantification.
Assessed cell viability to ensure no significant apoptosis effects during the experiments.
Most gene knockdowns increased EV secretion, with KRAS and BRAF knockdown leading to significant increases in P14 EV levels.
KRAS knockdown resulted in larger EV sizes and higher EV marker expression.
CTNNB1 downregulation increased P14 while decreasing P100 EV secretion.
CDH1 silencing reduced P14 EV levels while slightly increasing P100 EV levels.
No significant differences in effects on EV secretion between tumor suppressor genes and (proto-)oncogenes were observed.

Pätzold et al. (2026) studied this question.

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Loss-of-function screen identifies gene impacts on EV secretion in colorectal cancer cells, suggesting key signaling pathways are involved.