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 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.
['Zacharopoulou|Nefeli|N|', 'Tsapara|Anna|A|', 'Kallergi|Galatea|G|', 'Schmid|Evi|E|', 'Alkahtani|Saad|S|', 'Alarifi|Saud|S|', 'Tsichlis|Philip N|PN|', 'Kampranis|Sotirios C|SC|', 'Stournaras|Christos|C|']
D003110:Colonic Neoplasms D000071221:Enhancer of Zeste Homolog 2 Protein D044127:Epigenesis, Genetic D058750:Epithelial-Mesenchymal Transition D044783:F-Box Proteins D015972:Gene Expression Regulation, Neoplastic D045325:HCT116 Cells D006801:Humans D056484:Jumonji Domain-Containing Histone Demethylases D020559:Monomeric GTP-Binding Proteins
KDM2B EMT Small-GTPases Colon cancer