The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells
Background/Aims: The epigenetic factor KDM2B is a histone demethylase expressed in various tumors. Recently, we have shown that KDM2B regulates actin cytoskeleton organization, small Rho GTPases signaling, cell-cell adhesion and migration of prostate tumor cells. In the present study, we addressed i...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2018-05-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/489917 |
| _version_ | 1811281778972819456 |
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| author | Nefeli Zacharopoulou Anna Tsapara Galatea Kallergi Evi Schmid Saad Alkahtani Saud Alarifi Philip N. Tsichlis Sotirios C. Kampranis Christos Stournaras |
| author_facet | Nefeli Zacharopoulou Anna Tsapara Galatea Kallergi Evi Schmid Saad Alkahtani Saud Alarifi Philip N. Tsichlis Sotirios C. Kampranis Christos Stournaras |
| author_sort | Nefeli Zacharopoulou |
| collection | DOAJ |
| description | Background/Aims: The epigenetic factor KDM2B is a histone demethylase expressed in various tumors. Recently, we have shown that KDM2B regulates actin cytoskeleton organization, small Rho GTPases signaling, cell-cell adhesion and migration of prostate tumor cells. In the present study, we addressed its role in regulating EMT and small GTPases expression in colon tumor cells. Methods: We used RT-PCR for the transcriptional analysis of various genes, Western blotting for the assessment of protein expression and immunofluorescence microscopy for visualization of fluorescently labeled proteins. Results: We report here that KDM2B regulates EZH2 and BMI1 in HCT116 colon tumor cells. Knockdown of this epigenetic factor induced potent up-regulation of the protein levels of the epithelial markers E-cadherin and ZO-1, while the mesenchymal marker N-cadherin was downregulated. On the other hand, KDM2B overexpression downregulated the levels of both epithelial markers and upregulated the mesenchymal marker, suggesting control of EMT by KDM2B. In addition, RhoA, RhoB and RhoC protein levels diminished upon KDM2B-knockdown, while all three small GTPases became upregulated in KDM2B-overexpressing HCT116 cell clones. Interestingly, Rac1 GTPase level increased upon KDM2B-knockdown and diminished in KDM2B-overexpressing HCT116 colon tumor- and DU-145 prostate cancer cells. Conclusions: These results establish a clear functional role of the epigenetic factor KDM2B in the regulation of EMT and small-GTPases expression in colon tumor cells and further support the recently postulated oncogenic role of this histone demethylase in various tumors. |
| first_indexed | 2024-04-13T01:39:43Z |
| format | Article |
| id | doaj.art-8cef26e9a45c4b9086ba25ab811caabd |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-13T01:39:43Z |
| publishDate | 2018-05-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-8cef26e9a45c4b9086ba25ab811caabd2022-12-22T03:08:13ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-05-0147136837710.1159/000489917489917The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor CellsNefeli ZacharopoulouAnna TsaparaGalatea KallergiEvi SchmidSaad AlkahtaniSaud AlarifiPhilip N. TsichlisSotirios C. KampranisChristos StournarasBackground/Aims: The epigenetic factor KDM2B is a histone demethylase expressed in various tumors. Recently, we have shown that KDM2B regulates actin cytoskeleton organization, small Rho GTPases signaling, cell-cell adhesion and migration of prostate tumor cells. In the present study, we addressed its role in regulating EMT and small GTPases expression in colon tumor cells. Methods: We used RT-PCR for the transcriptional analysis of various genes, Western blotting for the assessment of protein expression and immunofluorescence microscopy for visualization of fluorescently labeled proteins. Results: We report here that KDM2B regulates EZH2 and BMI1 in HCT116 colon tumor cells. Knockdown of this epigenetic factor induced potent up-regulation of the protein levels of the epithelial markers E-cadherin and ZO-1, while the mesenchymal marker N-cadherin was downregulated. On the other hand, KDM2B overexpression downregulated the levels of both epithelial markers and upregulated the mesenchymal marker, suggesting control of EMT by KDM2B. In addition, RhoA, RhoB and RhoC protein levels diminished upon KDM2B-knockdown, while all three small GTPases became upregulated in KDM2B-overexpressing HCT116 cell clones. Interestingly, Rac1 GTPase level increased upon KDM2B-knockdown and diminished in KDM2B-overexpressing HCT116 colon tumor- and DU-145 prostate cancer cells. Conclusions: These results establish a clear functional role of the epigenetic factor KDM2B in the regulation of EMT and small-GTPases expression in colon tumor cells and further support the recently postulated oncogenic role of this histone demethylase in various tumors.https://www.karger.com/Article/FullText/489917Colon cancerKDM2BSmall-GTPasesEMT |
| spellingShingle | Nefeli Zacharopoulou Anna Tsapara Galatea Kallergi Evi Schmid Saad Alkahtani Saud Alarifi Philip N. Tsichlis Sotirios C. Kampranis Christos Stournaras The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells Cellular Physiology and Biochemistry Colon cancer KDM2B Small-GTPases EMT |
| title | The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells |
| title_full | The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells |
| title_fullStr | The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells |
| title_full_unstemmed | The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells |
| title_short | The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells |
| title_sort | epigenetic factor kdm2b regulates emt and small gtpases in colon tumor cells |
| topic | Colon cancer KDM2B Small-GTPases EMT |
| url | https://www.karger.com/Article/FullText/489917 |
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