Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53

Lee, Ji Yeon; Mustafa, Muhammad; Kim, Clara Yuri; Kim, Myoung Hee

doi:10.7150/jca.18818

Cited by 15 publications

(26 citation statements)

References 18 publications

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“…Interestingly, high ratio of CTCF/TP53 was accompanied by a shorter disease free survival time while the prognosis of the high TP53/CTCF ratio group was good ( Supplementary Figure 5C ). A previous study [ 27 ] identified CTCF binding site (CBS) in the promoter region approximately 800 bp upstream of the P53 transcription start site ( Figure 6D ). Therefore, ChIP-qPCR and ChIP-PCR assays were performed to confirm whether CTCF can bind to the site in CRC ( Supplementary Figure 6A and Figure 6F ).…”

Section: Resultsmentioning

confidence: 87%

“…GSEA revealed that CTCF expression is closely related to P53-related gene set signatures. A previous study reported that CTCF transcriptionally inhibits P53 in breast cancer [ 27 ]. Hence, we performed qRT-PCR, ChIP and dual luciferase reporter assays to investigate whether the regulatory mechanism between CTCF and P53 also exists in CRC cells.…”

Section: Discussionmentioning

confidence: 99%

“…As a multifunctional transcription factor, CTCF was reported to be involved in the initiation of multiple cancers, including breast cancer [ 18 ], hepatocellular carcinoma [ 22 ], lung cancer [ 14 ], prostate cancer [ 23 ], etc., which could be attributed to the abnormal expression of CTCF or the dysregulation of its target genes. Some common observations involving CTCF function in cancers include the transcriptional activation of TERT, c-MYC, FOXM1, PLK, GAD1 and other genes [ 14 , 22 , 24 – 26 ] and the transcriptional repression of p53, BCL6, RASSF1A, CDH1 and others [ 27 – 30 ]. Additionally, chromatin immunoprecipitation (ChIP)-PCR analysis revealed that CTCF affects a number of metastasis-associated genes, including CTBP1, SERPINE1 and SRC [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

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CTCF promotes colorectal cancer cell proliferation and chemotherapy resistance to 5-FU via the P53-Hedgehog axis

Lai

et al. 2020

Aging

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CTCF is overexpressed in several cancers and plays crucial roles in regulating aggressiveness, but little is known about whether CTCF drives colorectal cancer progression. Here, we identified a tumor-promoting role for CTCF in colorectal cancer. Our study demonstrated that CTCF was upregulated in colorectal cancer specimens compared with adjacent noncancerous colorectal tissues. The overexpression of CTCF promoted colorectal cancer cell proliferation and tumor growth, while the opposite effects were observed in CTCF knockdown cells. Increased GLI1, Shh, PTCH1, and PTCH2 levels were observed in CTCF-overexpressing cells using western blot analyses. CCK-8 and apoptosis assays revealed that 5-fluorouracil chemosensitivity was negatively associated with CTCF expression. Furthermore, we identified that P53 is a direct transcriptional target gene of CTCF in colorectal cancer. Western blot and nuclear extract assays showed that inhibition of P53 can counteract Hedgehog signaling pathway repression induced by CTCF knockdown. In conclusion, we uncovered a crucial role for CTCF regulation that possibly involves the P53-Hedgehog axis and highlighted the clinical utility of colorectal cancer-specific potential therapeutic target as disease progression or clinical response biomarkers.

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Section: Resultsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CTCF promotes colorectal cancer cell proliferation and chemotherapy resistance to 5-FU via the P53-Hedgehog axis

Lai

et al. 2020

Aging

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“…Interestingly, the effect of mutations on CTCF binding was found to be non-uniform, for instance different mutations in its zinc finger 3 domain led to selective inhibition of binding to different targets suggesting that there is a tumor-specific change of function rather than loss of function 38 . Furthermore, CTCF was shown to be elevated in breast cancer cell lines and breast tumors 39 , its overexpression was suggested to protect tumor cells from induction of apoptotic cell death 40 while its downregulation in breast cancer cell lines was shown to be associated with reduced cell proliferation 41,42 , both effects via transcriptional regulation of target genes. In line with these results we find overall increased chromatin binding of CTCF in G12V MCF10A cells, although without detectable elevation in its gene expression levels.…”

Section: Discussionmentioning

confidence: 99%

Genomic Retargeting of Tumor Suppressors p53 and CTCF Promotes Oncogenesis

Schwartz

et al. 2019

Preprint

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Gene transcription is substantially regulated by distant regulatory elements via combinatorial binding of transcription factors. It is more and more recognized that alterations in chromatin state and transcription factor binding in these distant regulatory elements may have key roles in cancer development. Here we focused on the first stages of oncogene induced carcinogenic transformation, and characterized the regulatory network underlying transcriptional reprogramming associated with this process. Using Hi-C data, we couple between differentially expressed genes and their differentially active regulatory elements and reveal two candidate transcription factors, p53 and CTCF, as major determinants of transcriptional reprogramming at early stages of HRas-induced transformation.Strikingly, the malignant transcriptional reprograming is promoted by redistribution of chromatin binding of these factors without major variation in their expression level. Our results demonstrate that alterations in the regulatory landscape have a major role in driving oncogene-induced transcriptional reprogramming.

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“…CTCF can act as both tumor suppressor and oncogene depending on the type of cancer (229, 230). In ovarian cancer, CTCF expression is upregulated and shows association with poor prognosis (231).…”

Section: Classification Of Mbpsmentioning

confidence: 99%

DNA Methylation Readers and Cancer: Mechanistic and Therapeutic Applications

2019

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DNA methylation is a major epigenetic process that regulates chromatin structure which causes transcriptional activation or repression of genes in a context-dependent manner. In general, DNA methylation takes place when methyl groups are added to the appropriate bases on the genome by the action of “writer” molecules known as DNA methyltransferases. How these methylation marks are read and interpreted into different functionalities represents one of the main mechanisms through which the genes are switched “ON” or “OFF” and typically involves different types of “reader” proteins that can recognize and bind to the methylated regions. A tightly balanced regulation exists between the “writers” and “readers” in order to mediate normal cellular functions. However, alterations in normal methylation pattern is a typical hallmark of cancer which alters the way methylation marks are written, read and interpreted in different disease states. This unique characteristic of DNA methylation “readers” has identified them as attractive therapeutic targets. In this review, we describe the current state of knowledge on the different classes of DNA methylation “readers” identified thus far along with their normal biological functions, describe how they are dysregulated in cancer, and discuss the various anti-cancer therapies that are currently being developed and evaluated for targeting these proteins.

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Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53

Cited by 15 publications

References 18 publications

CTCF promotes colorectal cancer cell proliferation and chemotherapy resistance to 5-FU via the P53-Hedgehog axis

CTCF promotes colorectal cancer cell proliferation and chemotherapy resistance to 5-FU via the P53-Hedgehog axis

Genomic Retargeting of Tumor Suppressors p53 and CTCF Promotes Oncogenesis

DNA Methylation Readers and Cancer: Mechanistic and Therapeutic Applications

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