Jong Seog Ahn
Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, (KRIBB) Ochang, Korea
Secondary metabolites produced by microorganisms have proven to be a valuable repository of natural bioactive compounds and many of them have been identified as useful research reagents and potential drug candidates. Fusarisetin A (FSA), a secondary metabolite with an unprecedented 6,6,5,5,5-fused pentacyclic ring structure, is generated by the soil fungus Fusarium sp. FN080326. FSA shows a potential for anti-metastatic agent with anti-invasive and anti-migratory activities against tumour cells.
By the pull-down of cell lysate using FSA-immobilized beads, Chromosome segregation 1-like (CSE1L) was identified as a molecular target of FSA. The gene knock out (siRNA and shRNA) and over-expression for the CSE1L in MDAMB- 231 cells showed the same phenotypic effects of FSA treatment such as inhibition of tumor cell invasion. CSE1L also known as exportin-2 is a nuclear-export receptor that mediates the nucleocytoplasmic recycling of importin α. Moreover, FSA induced a dose-dependent accumulation of importin α in the nucleus by disrupting CSE1L-importin α interaction. So, we suggest that FSA has a potential for anti-metastatic agent and the cellular binding protein, CSE1L, can be explored as a new molecular target for cancer metastasis.
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