title: Microcystin-LR promotes epithelial-mesenchymal transition in colorectal cancer cells through PI3-K/AKT and SMAD2.
abstract: 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.
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
authors.forename: Mengli
authors.initials: M
authors.lastname: Yang
authors.affiliation: Departments of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA; Department of Cellular, Molecular, and Biomedical Sciences, University of New Hampshire, Rudman Hall, 46 College Road, Durham, NH 03824, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
authors.forename: Qiangqiang
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China. Electronic address: wangting@njmu.edu.cn.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D019073:HT29 Cells; D006801:Humans; D008387:Marine Toxins; D052998:Microcystins / Q000633:toxicity*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D008387:Marine Toxins; D052998:Microcystins; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D014874:Water Pollutants, Chemical; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C057862:cyanoginosin LR
keywords: Colorectal cancer; EMT; Microcystin-LR; PI3-K/AKT; SMAD2