Twist1-induced epithelial-mesenchymal transition according to microsatellite instability status in colon cancer cells

• Published in: Oncotarget 2016-08, Vol.7 (35), p.57066-57076
• Main Authors: Oh, Bo Young, Kim, So-Young, Lee, Yeo Song, Hong, Hye Kyung, Kim, Tae Won, Kim, Seok Hyung, Lee, Woo Yong, Cho, Yong Beom
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - chemistry; Antigens, CD - metabolism; Cell Adhesion Molecules, Neuronal - metabolism; Cell Count; Cell Line, Tumor; Cell Movement; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Epithelial-Mesenchymal Transition; Female; Fetal Proteins - metabolism; Glycogen Synthase Kinase 3 beta - metabolism; Humans; Hyaluronan Receptors - metabolism; Mice; Mice, Inbred BALB C; Microsatellite Instability; Neoplasm Transplantation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Research Paper; Signal Transduction; Stem Cells - metabolism; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.10974

Colorectal cancer (CRC) with microsatellite instability (MSI) may exhibit impaired epithelial-mesenchymal transition (EMT), but little is known about the underlying mechanisms of this phenomenon. In this study, we investigated the role of Twist1 and its downstream signaling cascades in EMT induction according to MSI status. To investigate the effects of Twist1 on EMT induction according to MSI status, MSS LS513 and MSI LoVo colon cancer cell lines, which overexpress human Twist1, were generated. Twist1-induced EMT and its downstream signaling pathways were evaluated via in vitro and in vivo experiments. We found that Twist1 induced EMT markers and stem cell-like characteristics via AKT signaling pathways. Twist1 induced activation of AKT and suppression of glycogen synthase kinase (GSK)-3β, which resulted in the activation of β-catenin, increasing CD44 expression. In addition, Twist1 activated the AKT-induced NF-κB pathway, increasing CD44 and CD166 expression. Activation of both the AKT/GSK-3β/β-catenin and AKT/NF-κB pathways occurred in MSS LS513 cells, while only the AKT/GSK-3β/β-catenin pathway was activated in MSI LoVo cells. In conclusion, Twist1 induces stem cell-like characteristics in colon cancer cell lines related to EMT via AKT signaling pathways, and those pathways depend on MSI status.