Research Papers:

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

Bo Young Oh, So-Young Kim, Yeo Song Lee, Hye Kyung Hong, Tae Won Kim, Seok Hyung Kim, Woo Yong Lee and Yong Beom Cho _

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Oncotarget. 2016; 7:57066-57076. https://doi.org/10.18632/oncotarget.10974

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Bo Young Oh1,*, So-Young Kim2,*, Yeo Song Lee2, Hye Kyung Hong2, Tae Won Kim4, Seok Hyung Kim3, Woo Yong Lee1,4, Yong Beom Cho1,4,5

1Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea

3Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

4Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea

5Department of Medical Device Management & Research, SAIHST, Sungkyunkwan University, Seoul, Korea

*These authors have contributed equally to this work

Correspondence to:

Yong Beom Cho, email: gscyb@skku.edu

Woo Yong Lee, email: lwy555@skku.edu

Keywords: Twist1, epithelial to mesenchymal transition, microsatellite instability, colorectal cancer

Received: December 15, 2015    Accepted: July 18, 2016    Published: August 01, 2016


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.

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