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High-Throughput Screening of Cancer Cluster Metastasis Inhibitors [Human]

ABSTRACT: Extravasation is a pivotal step in cancer metastasis, however, no molecular control of cancer extravasation has yet been achieved because the mechanism behind this process remain poorly understood. Here, we identify Bay 61-3606 as cancer extravasation inhibitor using high throughput drug screening. Bay 61-3606 significantly decreases cancer cluster extravasation, which is associated with higher metastasis potential, in a zebrafish model. This inhibitory effect extends to decreased distant metastasis in a murine lung carcinoma model and a triple-negative breast cancer model. In addition, our RNA-sequencing results reveal the essential role of COL8A1, a cell-adhesion related molecule expressed by the extravasation participating endothelial cells, in cancer cluster extravasation. Bay 61-3606 treatment effectively decreases COL8A1 through JNK signaling pathway, resulting in impaired cancer cluster extravasation. As the infiltration of immune cells is independent on COL8A1, our findings suggest Bay 61-3606 is a potent drug for anti-metastasis therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE243084 | GEO | 2026/08/26

REPOSITORIES: GEO

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High-Throughput Screening of Cancer Cluster Metastasis Inhibitors

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