Abstract LB-186: <i>Twist-1</i> overexpression modulates cancer progression according to the microsatellite instability status in colorectal cancer cell lines
Authors: Sungwon Jung, Hye Kyung Hong, Bo Young Oh, So Young Kim, Heunmin Song, Heewon Park, Woo Yong Lee, Yong Beom Cho
Journal: Cancer Research (2014)

Abstract Background: The Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal cells. EMT has also been shown to occur in the initiation of metastasis for cancer progression. Twist-1 has driving effects in cancer metastasis and is involved in the process of EMT. Overexpression of Twist-1 is common in metastatic carcinomas. Moreover, Twist-1 plays an important role in some physiological processes involved in metastasis, like tumor cell migration, angiogenesis, invasion, chromosomal instability and maintenance of cancer stem cells via the induction of EMT. In this study, we evaluated if Twist-1 and its downstream signaling cascades induced activation of EMT according to the microsatellite instability status in colon cancer cell lines. Methods: To understand this mechanism, LS513 (MSS) and LoVo (MSI) cells were transfected with Twist-1-pCMV plasmids and GFP-pCMV plasmid was used as negative control. Western blots were used to detect expression of EMT related proteins. Cell proliferation assay, cell migration assay, cell invasion assay, and colony forming assay were used to confirm the metastatic effect by Twist-1 overexpression. Also, we examined tumorigenesis assay in vivo to evaluate cancer growth induced by Twist-1 overexpression. Results: The expression of E-cadherin was down-regulated, but that of vimentin was up-regulated in both Twist overexpressed-LS513 and LoVo cell lines. There were mesenchymal morphological changes such as spindle like shape in both cell lines. We found that overexpression of Twist-1 induced downregulation of E-cadherin and upregulation of β-catenin via AKT phosphorylation in these cells. Also, we identified the upregulation of NF-kB as a mediator of the cancer progression in Twist-1 overexpressed LS513 cells. However, the expression of NF-kB decreased in Twist-1 overexpressed LoVo cell lines. Cell proliferation, migration, invasion and in vivo tumorigenecity were increased more in Twist-1 activated cells than negative control cells in LS513 cell line. However, there were no differences of colony forming assay and in vivo tumor growth between Twist-1 activated cells and negative control cells in LoVo cell line although cell proliferation, cell migration, and cell invasion were increased in Twist-1 activated cell lines. Conclusion: Twist-1 overexpression could induce activation of EMT in colon cancer cell lines. NF-kB played as a mediator of cancer progression in Twist-1 overexpressed LS513 (MSS) cells. But, NF-kB expression was down-regulated in Twist-1 overexpressed-LoVo (MSI) cells. These results suggest that upregulation of Twist-1 is associated with colon cancer progression via activation of NF-kB signaling pathway in MSS colon cancers but not in MSI colon cancers. Citation Format: Sungwon Jung, Hye Kyung Hong, Bo Young Oh, So Young Kim, Heunmin Song, Heewon Park, Woo Yong Lee, Yong Beom Cho. Twist-1 overexpression modulates cancer progression according to the microsatellite instability status in colorectal cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-186. doi:10.1158/1538-7445.AM2014-LB-186