Zebrafish embryo screen identifies anti-metastasis drugs [article]

Joji Nakayama, Lora Tan, Boon Cher Goh, Shu Wang, Hideki Makinoshima, Gong Zhiyuan
2021 bioRxiv   pre-print
Metastasis is responsible for approximately 90% of cancer-associated mortality, but few models exist that allow for rapid and effective screening of anti-metastasis drugs. Here we report a novel screening concept utilizing conserved mechanisms between metastasis and zebrafish gastrulation for identifying anti-metastasis drugs. Molecular mechanisms involved in metastasis and vertebrate gastrulation are conserved; at least fifty common genes play essential roles in governing these mechanisms. We
more » ... ypothesized that small chemicals that interrupt zebrafish gastrulation might also suppress metastatic progression of cancer cells and developed a phenotype-based chemical screen to test the hypothesis. The screen used epiboly, the first morphogenetic movement in gastrulation as a marker, and identified a serotonin receptor 2C (HTR2C) antagonist as an epiboly-interrupting drug. A mouse model of metastasis confirmed that pharmacologic and genetic inhibition of HTR2C suppressed metastasis. Taken together, this screen could offer a rapid and high-throughput platform for discovery of anti-metastasis drugs.
doi:10.1101/2021.03.04.434001 fatcat:srwhs77pujgelczk7jik4hzdpq