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Published on: April 22, 2019
Decreased syndecan-2 expression correlates with trichostatin-A induced-morphological changes and reduced tumorigenic
Yeonhee Kim1, Haein Park, Yangmi Lim
1Department of Life Sciences, Division of Molecular Life Sciences and Center for Cell Signalling Research, Ewha Womans University, Seoul, Korea.
Abstract:
The inhibition of histone deacetylase activity is known to induce morphological changes of transformed cells. In this study, we investigated the effect of the specific HDAC inhibitor, trichostatin A (TSA), on colon carcinoma cell lines. Treatment of human colorectal carcinoma cells, KM1214 and KM12SM, with TSA induced distinct morphological changes. Both cell lines, which normally piled up in layers without clear boundary, became more flattened, and formed monolayers with evident boundaries between cells, with concomitant increased actin filament organization. Cell-cell interaction was not affected much, based on expression level, membrane localization, and interaction of E-cadherin with beta-catenin. In contrast, syndecan-2 expression was dramatically reduced and it was correlated with the morphological changes of colon carcinoma cells. Consistently, downregulation of syndecan-2 expression by antisense cDNA clearly mimicked the morphological changes in KM12SM and reduced anchorage-independent growth of colon cancer cells. All these results indicate that reduced syndecan-2 expression correlates with TSA-induced morphological changes and reduced tumorigenic activity in colon carcinoma cells.
Insights
Histone deacetylase inhibitor trichostatin A (TSA) alters colon carcinoma cell morphology. Reduced syndecan-2 expression correlates with these changes and decreased tumor cell growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Histone deacetylase (HDAC) inhibition is known to induce morphological alterations in transformed cells.
- Colon carcinoma cell lines exhibit characteristic growth patterns that can be modulated by external factors.
Purpose of the Study:
- To investigate the specific effects of trichostatin A (TSA), a histone deacetylase inhibitor, on the morphology of colon carcinoma cell lines.
- To explore the correlation between TSA-induced morphological changes and the expression of syndecan-2.
Main Methods:
- Treatment of human colorectal carcinoma cell lines (KM1214 and KM12SM) with trichostatin A (TSA).
- Assessment of cell morphology, actin filament organization, and expression/localization of E-cadherin and beta-catenin.
- Analysis of syndecan-2 expression levels and its role via antisense cDNA downregulation.
- Evaluation of anchorage-independent growth.
Main Results:
- TSA treatment induced distinct morphological changes in colon carcinoma cells, leading to flattened monolayers with clear cell boundaries and increased actin organization.
- Syndecan-2 expression was dramatically reduced following TSA treatment, correlating with the observed morphological shifts.
- Downregulation of syndecan-2 expression mimicked TSA-induced morphological changes and reduced anchorage-independent growth.
Conclusions:
- Reduced syndecan-2 expression is closely associated with TSA-induced morphological alterations in colon carcinoma cells.
- The modulation of syndecan-2 expression by HDAC inhibition may contribute to reduced tumorigenic activity in colon cancer.
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