KDM4C Activity Modulates Cell Proliferation and Chromosome Segregation in Triple-Negative Breast Cancer

Abstract

The Jumonji-containing domain protein, KDM4C, is a histone demethylase associated with the development of several forms of human cancer. However, its specific function in the viability of tumoral lineages is yet to be determined. This work investigates the importance of KDM4C activity in cell proliferation and chromosome segregation of three triple-negative breast cancer cell lines using a specific demethylase inhibitor. Immunofluorescence assays show that KDM4C is recruited to mitotic chromosomes and that the modulation of its activity increases the number of mitotic segregation errors. However, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) cell proliferation assays demonstrate that the demethylase activity is required for cell viability. These results suggest that the histone demethylase activity of KDM4C is essential for breast cancer progression given its role in the maintenance of chromosomal stability and cell growth, thus highlighting it as a potential therapeutic target.

circZMYM2 Competed Endogenously with miR-335-5p to Regulate JMJD2C in Pancreatic Cancer

“…Furthermore, JMJD2C expression was found to be higher in metastatic than in non-metastatic lung cancer tissues [10]. The histone demethylase activity of JMJD2C was essential for breast cancer progression given its role in the maintenance of chromosomal stability and cell growth, further highlighting its potential of becoming a therapeutic target [9]. Overexpression of JMJD2C also conferred a pro-growth effect on colon carcinoma cells.…”

“…As part of JMJ family, the members belonging to its subset JMJD2/KDM4 are associated with pancreatic cancer development, tumor cell development and proliferation, as well as progression of abnormal cells to an invasive and highly metastatic form by regulating their migratory and invasive capacities [9]. Many studies have put forward that JMJD2C is associated with lung cancer [10], breast cancer (triple-negative) [9], colon cancer [11], and so on. The role of JMJD2C in pancreatic cancer mechanism could also be explored.…”

iPSC-derived Cancer Organoids Recapitulate Genomic and Phenotypic Alterations of c-met-mutated Hereditary Kidney Cancer

“…5g). KDM4C is a member of the Jumonji-domain 2 family encoding a demethylase involved in chromosome segregation 26 . Alteration of KDM4C gene has been shown to occur in renal cell carcinoma 27 .…”

Advances in histone demethylase KDM4 as cancer therapeutic targets

“…KDM4C activity is also important in chromosome segregation of triple‐negative breast cancer cell lines . KDM4C is recruited to mitotic chromosomes and regulates the number of mitotic segregation errors, thereby modulating chromosomal stability …”

“…KDM4C activity is also important in chromosome segregation of triple-negative breast cancer cell lines. 133 KDM4C is recruited to mitotic chromosomes and regulates the number of mitotic segregation errors, thereby modulating chromosomal stability. 131 KDM4C is also cleaved by the apoptotic effector protease caspase-3 within the DEVD396G motif, which causes loss of demethylating enzyme activity in the DEVD396G motif.…”