The histone demethylase KDM2B activates FAK and PI3K that control tumor cell motility.

Abstract

Recent studies revealed that the histone demethylase KDM2B regulates the epithelial markers E-Cadherin and ZO-1, the RhoA/B/C-small-GTPases and actin cytoskeleton organization, in DU-145 prostate- and HCT-116 colon-tumor cells. Here we addressed the role of KDM2B in the activation of Focal Adhesion Kinase (FAK)-signaling and its involvement in regulating tumor cell motility. We used RT-PCR for gene transcriptional analysis, Western blotting for the assessment of protein expression and activity and wound-healing assay for the study of cell migration. KDM2B overexpression or silencing controls the activity of FAK in DU-145 prostate- and HCT-116 colon-tumor cells without affecting gene transcription and protein expression of this kinase. Upon KDM2B overexpression in DU-145 cells, significantly enhanced migration was observed, which was abolished in cells pretreated by the specific phosphoinositide-3 kinase (PI3 K) inhibitor LY294002, implying involvement of FAK/PI3 K signaling in the migration process. In line with this, the p85-PI3 K-subunit was downregulated upon knockdown of KDM2B in DU-145 cells, while the opposite effect became evident in KDM2B-overexpressing cells. These results revealed a novel functional role of KDM2B in regulating the activation of the FAK/PI3 K signaling in prostate cancer cells that participates in the control of cell motility.

• Authors: Nefeli Zacharopoulou, Galatea Kallergi, Saad Alkahtani, Anna Tsapara, Saud Alarifi, Evi Schmid, Basma Sukkar, Sotirios Kampranis, Florian Lang, Christos Stournaras
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 21 Issue 6 Pg. 533-540 (06 02 2020) ISSN: 1555-8576 [Electronic] United States
• PMID: 32175798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• F-Box Proteins
• Jumonji Domain-Containing Histone Demethylases
• KDM2A protein, human
• Focal Adhesion Kinase 2
• PTK2B protein, human

Topics

• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Cell Movement
• Cell Proliferation
• Colonic Neoplasms (genetics, metabolism, pathology)
• F-Box Proteins (genetics, metabolism)
• Focal Adhesion Kinase 2 (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Jumonji Domain-Containing Histone Demethylases (genetics, metabolism)
• Male
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Prostatic Neoplasms (genetics, metabolism, pathology)
• Tumor Cells, Cultured