Microcystin-LR promotes epithelial-mesenchymal transition in colorectal cancer cells through PI3-K/AKT and SMAD2.

Increasing evidences suggest that microcystins, a kind of toxic metabolites, produced by cyanobacteria in contaminated water may contribute to the aggravation of the human colorectal carcinoma. Our previous study showed that microcystin-LR (MC-LR) exposure caused significant invasion and migration of colorectal cancer cells. However, the roles of MC-LR in regulating epithelial-mesenchymal transition (EMT) in colorectal cancer cells remain unknown. In our study, we observed that MC-LR treatment decreased epithelial marker E-cadherin expression and up-regulated the levels of mesenchymal markers Vimentin and Snail in colorectal cancer cells. Moreover, MC-LR stimulated protein expression of SMAD2 and phospho-SMAD2 by PI3-K/AKT activation. The activated PI3-K/AKT and SMAD2 signaling largely accounted for MC-LR-induced EMT, which could be reversed by SMAD2 RNA interference or PI3-K/AKT chemical inhibitor in colorectal cancer cells. Our results show that MC-LR could induce SMAD2 expression to promote colorectal cancer cells EMT, which not only provides a mechanistic insight on MC-LR promotes EMT in colorectal cancer cells, but also support to the development of therapies aimed at SMAD2 in colorectal cancer induced by MC-LR.