Histone demethylase KDM7A is required for stem cell maintenance and apoptosis inhibition in breast cancer

Meng, Zhenzhen; Liu, Ying; Wang, Jie; Fan, Hua-Ying; Fang, Huan; Li, Sha; Yuan, Lin; Liu, Cuicui; Peng, You; Zhao, Weiwei; Wang, Lulu; Li, Jing; Feng, Jing

doi:10.1002/jcp.29008

Cited by 29 publications

(22 citation statements)

References 36 publications

(53 reference statements)

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“…This is because the AR expression level of the cell lines that we used was notably lower than that of prostate cancer, and the repressive effect on neoplasia was relatively strong. Factors other than AR may include KLF4 and c-MYC, which were found to be involved in breast cancer stem cell maintenance [34]. The use of only two bladder cell lines with undifferentiated character may also limit the universality of our data.…”

Section: Discussionmentioning

confidence: 92%

“…Since the methylation of H3K9 and H3K27 represent the repression of gene expression, their demethylation activates target gene transcription. Previous studies have shown that KDM7A regulates bone development, adipogenesis, inflammation, as well as the development of various types of cancers [ 34 , 35 , 36 ]. A recently published paper from our research group described the H3K27 demethylase activity of KDM7A on the response elements of AR target genes in prostate cancer [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

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Histone Demethylase KDM7A Regulates Androgen Receptor Activity, and Its Chemical Inhibitor TC-E 5002 Overcomes Cisplatin-Resistance in Bladder Cancer Cells

Lee

Kim

Jeong

et al. 2020

IJMS

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Histone demethylase KDM7A regulates many biological processes, including differentiation, development, and the growth of several cancer cells. Here, we have focused on the role of KDM7A in bladder cancer cells, especially under drug-resistant conditions. When the KDM7A gene was knocked down, bladder cancer cell lines showed impaired cell growth, increased cell death, and reduced rates of cell migration. Biochemical studies revealed that KDM7A knockdown in the bladder cancer cells repressed the activity of androgen receptor (AR) through epigenetic regulation. When we developed a cisplatin-resistant bladder cancer cell line, we found that AR expression was highly elevated. Upon treatment with TC-E 5002, a chemical inhibitor of KDM7A, the cisplatin-resistant bladder cancer cells, showed decreased cell proliferation. In the mouse xenograft model, KDM7A knockdown or treatment with its inhibitor reduced the growth of the bladder tumor. We also observed the upregulation of KDM7A expression in patients with bladder cancer. The findings suggest that histone demethylase KDM7A mediates the growth of bladder cancer. Moreover, our findings highlight the therapeutic potential of the KMD7A inhibitor, TC-E 5002, in patients with cisplatin-resistant bladder cancer.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Histone Demethylase KDM7A Regulates Androgen Receptor Activity, and Its Chemical Inhibitor TC-E 5002 Overcomes Cisplatin-Resistance in Bladder Cancer Cells

Lee

Kim

Jeong

et al. 2020

IJMS

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“…The NC, SETDB2-knockdown, SETDB2-rescued and ΔNp63α-rescued SUM159PT or MDA-MB-231 cells were subjected to a primary mammosphere assay according to a previously described protocol [24]. For the secondary mammosphere assay, primary mammospheres derived from SUM159PT cells were collected and digested in 2 mg/mL DNaseI (#10104159, Sigma-Aldrich, Germany) and 4 mg/mL collagenase type IV (#5138, Sigma-Aldrich, Germany), after which the cells were counted and seeded in ultra-low attachment plates according to a previously described protocol [24].…”

Section: Mammosphere Assaymentioning

confidence: 99%

“…The NC and SETDB2-knockdown SUM159PT and MDA-MB-231 cells were seeded and used for CCK-8 and colony formation assays according to a previously described protocol [24].…”

Section: Cell Proliferation and Colony Formation Assaysmentioning

confidence: 99%

SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of ΔNp63α protein

Liu¹,

Xie²,

Jialun³

et al. 2020

Int. J. Biol. Sci.

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The histone H3K9 methyltransferase SETDB2 is involved in cell cycle dysregulation in acute leukemia and has oncogenic roles in gastric cancer. In our study, we found that SETDB2 plays essential roles in breast cancer stem cell maintenance. Depleted SETDB2 significantly decreased the breast cancer stem cell population and mammosphere formation in vitro and also inhibited breast tumor initiation and growth in vivo. Restoring SETDB2 expression rescued the defect in breast cancer stem cell maintenance. A mechanistic analysis showed that SETDB2 upregulated the transcription of the ΔNp63α downstream Hedgehog pathway gene. SETDB2 also interacted with and methylated ΔNp63α, and stabilized ΔNp63α protein. Restoring ΔNp63α expression rescued the breast cancer stem cell maintenance defect which mediated by SETDB2 knockdown. In conclusion, our study reveals a novel function of SETDB2 in cancer stem cell maintenance in breast cancer.

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“…In many tumors, changes of histone demethylase expression have been identified as a key characteristic during cancer initiation and progression, suggesting that these genes might be functionally important for cancer development [ 9 ]. Indeed, histone demethylases, such as KDM3A and KDM6A, have been shown to be essential for maintenance of CSCs in several types of cancers [ 10 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Histone Demethylase KDM4C Is Required for Ovarian Cancer Stem Cell Maintenance

Ling

Zeng

Zhu

et al. 2020

Stem Cells International

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Ovarian cancer is a highly deadly disease, which is often diagnosed at a late stage with metastases. However, most ovarian cancers relapse after surgery combined with platinum-based chemotherapy. Cancer stem cells (CSCs) are stem-like cells that possess high tumorigenic capability and display higher resistant capability against current therapies. However, our knowledge of ovarian CSCs and their molecular mechanism remains sparse. In the current study, we found that KDM4C, a histone demethylase, was required for ovarian cancer stem cell (CSC) maintenance. Depletion of KDM4C significantly reduced the CSC population and sphere formation in vitro. Moreover, we found that KDM4C can regulate the expression of stem cell factor OCT-4 via binding to its promoter. These data indicate that KDM4C is relevant for ovarian CSC maintenance and underscore its importance as a potential therapeutic target.

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Histone demethylase KDM7A is required for stem cell maintenance and apoptosis inhibition in breast cancer

Cited by 29 publications

References 36 publications

Histone Demethylase KDM7A Regulates Androgen Receptor Activity, and Its Chemical Inhibitor TC-E 5002 Overcomes Cisplatin-Resistance in Bladder Cancer Cells

Histone Demethylase KDM7A Regulates Androgen Receptor Activity, and Its Chemical Inhibitor TC-E 5002 Overcomes Cisplatin-Resistance in Bladder Cancer Cells

SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of ΔNp63α protein

Histone Demethylase KDM4C Is Required for Ovarian Cancer Stem Cell Maintenance

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