title: IGF-1-induced epithelial-mesenchymal transition in MCF-7 cells is mediated by MUC1.
abstract: Metastases are the major cause of death from cancer. IGF-1 signaling pathway has been shown to have strong implication in the epithelial-mesenchymal transition (EMT) process. However, the mechanisms of how IGF-1 promotes EMT have not been fully elucidated. Mucin 1 (MUC1), a transmembrane glycoprotein, engages in multiple cancer-related signaling pathways and functions as an oncoprotein that contributes to metastases. Here we provide evidence showing that IGF-1 upregulates MUC1 expression in MCF-7 cells in a PI3K/Akt signaling pathway-dependent manner. The overexpression of MUC1 is critical for IGF-1-induced EMT of MCF-7 cells because the knockdown of MUC1 prevented the EMT of MCF-7 cells as demonstrated by various EMT markers including the expression of E-cadherin, N-cadherin, vimentin, fibronectin and the nuclear translocalization of β-catenin. On the other hand, the knockdown of MUC1 had no impact on IGF-1-induced activation of PI3K/Akt or MAPK. In summary, our study demonstrated MUC1 as a critical downstream effector that mediates IGF-1-induced EMT of MCF-7 cells and suggested that MUC1 might be a potential therapeutic target for preventing tumor metastases.
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China; Simcere Pharmaceutical Co., Ltd., Nanjing, Jiangsu, China; BioSciKin Co., Ltd., Nanjing, Jiangsu, China; MtC BioPharma Co., Ltd., Nanjing, Jiangsu, China.
authors: Gaoyong
authors: G
authors: Liao
authors: Simcere Pharmaceutical Co., Ltd., Nanjing, Jiangsu, China; BioSciKin Co., Ltd., Nanjing, Jiangsu, China; MtC BioPharma Co., Ltd., Nanjing, Jiangsu, China.
authors: Mengyu
authors: M
authors: Wang
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: ouyu2008@126.com.
authors: Yu
authors: Y
authors: Ou
authors: Simcere Pharmaceutical Co., Ltd., Nanjing, Jiangsu, China; BioSciKin Co., Ltd., Nanjing, Jiangsu, China; MtC BioPharma Co., Ltd., Nanjing, Jiangsu, China. Electronic address: zhaoyong@mtcbiopharma.com.
authors: Yong
authors: Y
authors: Zhao
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D061986:MCF-7 Cells; D009025:Morpholines / Q000494:pharmacology; D018396:Mucin-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D002070:Butadienes; D015820:Cadherins; D002867:Chromones; D007334:Insulin-Like Growth Factor I; D009025:Morpholines; D018396:Mucin-1; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D014746:Vimentin; D051176:beta Catenin; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: EMT; ERK; IGF-1; MUC1; Migration; PI3K/Akt