Anti-migration and anti-invasion effects of LY-290181 on breast cancer cell lines through the inhibition of Twist1
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Breast cancer has become the most common cancer amongwomen worldwide. Among breast cancers, metastatic breastcancer is associated with the highest mortality rate. Twist1,one of the epithelial-mesenchymal transition-regulating transcriptionfactors, is known to promote the intravasation ofbreast cancer cells into metastatic sites. Therefore, targetingTwist1 to develop anti-cancer drugs might be a valuable strategy. In this study, LY-290181 dose-dependently inhibited migration,invasion, and multicellular tumor spheroid invasion inbreast cancer cell lines. These anti-cancer effects of LY-290181were mediated through the down-regulation of Twist1 proteinlevels. LY-290181 inhibited extracellular signal-regulated kinaseand c-Jun N-terminal kinase signaling pathways. Therefore, ourfindings suggest that LY-290181 may serve as a basis for futureresearch and development of an anti-cancer agent targetingmetastatic cancers.
Abstract
Breast cancer has become the most common cancer amongwomen worldwide. Among breast cancers, metastatic breastcancer is associated with the highest mortality rate. Twist1,one of the epithelial-mesenchymal transition-regulating transcriptionfactors, is known to promote the intravasation ofbreast cancer cells into metastatic sites. Therefore, targetingTwist1 to develop anti-cancer drugs might be a valuable strategy. In this study, LY-290181 dose-dependently inhibited migration,invasion, and multicellular tumor spheroid invasion inbreast cancer cell lines. These anti-cancer effects of LY-290181were mediated through the down-regulation of Twist1 proteinlevels. LY-290181 inhibited extracellular signal-regulated kinaseand c-Jun N-terminal kinase signaling pathways. Therefore, ourfindings suggest that LY-290181 may serve as a basis for futureresearch and development of an anti-cancer agent targetingmetastatic cancers.
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