The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells

Nefeli Zacharopoulou; Anna Tsapara; Galatea Kallergi; Evi Schmid; Saad Alkahtani; Saud Alarifi; Philip N Tsichlis; S.C. Kampranis; Christos Stournaras

doi:10.1159/000489917

The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells

Nefeli Zacharopoulou, Anna Tsapara, Galatea Kallergi, Evi Schmid, Saad Alkahtani, Saud Alarifi, Philip N Tsichlis, S.C. Kampranis, Christos Stournaras

11 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Cellular Physiology and Biochemistry
Vol/bind	47
Udgave nummer	1
Sider (fra-til)	368-377
Antal sider	10
ISSN	1015-8987
DOI	https://doi.org/10.1159/000489917
Status	Udgivet - 1 jun. 2018
Udgivet eksternt	Ja

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10.1159/000489917

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@article{cee5ebb8890247aa96971d37e24798bd,

title = "The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells",

abstract = "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.",

keywords = "Colonic Neoplasms/genetics, Enhancer of Zeste Homolog 2 Protein/genetics, Epigenesis, Genetic, Epithelial-Mesenchymal Transition, F-Box Proteins/genetics, Gene Expression Regulation, Neoplastic, HCT116 Cells, Humans, Jumonji Domain-Containing Histone Demethylases/genetics, Monomeric GTP-Binding Proteins/genetics",

author = "Nefeli Zacharopoulou and Anna Tsapara and Galatea Kallergi and Evi Schmid and Saad Alkahtani and Saud Alarifi and Tsichlis, {Philip N} and S.C. Kampranis and Christos Stournaras",

year = "2018",

month = jun,

day = "1",

doi = "10.1159/000489917",

language = "English",

volume = "47",

pages = "368--377",

journal = "Cellular Physiology and Biochemistry",

issn = "1015-8987",

publisher = "S Karger AG",

number = "1",

}

TY - JOUR

T1 - The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells

AU - Zacharopoulou, Nefeli

AU - Tsapara, Anna

AU - Kallergi, Galatea

AU - Schmid, Evi

AU - Alkahtani, Saad

AU - Alarifi, Saud

AU - Tsichlis, Philip N

AU - Kampranis, S.C.

AU - Stournaras, Christos

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

KW - Colonic Neoplasms/genetics

KW - Enhancer of Zeste Homolog 2 Protein/genetics

KW - Epigenesis, Genetic

KW - Epithelial-Mesenchymal Transition

KW - F-Box Proteins/genetics

KW - Gene Expression Regulation, Neoplastic

KW - HCT116 Cells

KW - Humans

KW - Jumonji Domain-Containing Histone Demethylases/genetics

KW - Monomeric GTP-Binding Proteins/genetics

U2 - 10.1159/000489917

DO - 10.1159/000489917

M3 - Journal article

C2 - 29772566

SN - 1015-8987

VL - 47

SP - 368

EP - 377

JO - Cellular Physiology and Biochemistry

JF - Cellular Physiology and Biochemistry

IS - 1

ER -

The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells

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