TET1 Exerts Its Tumor Suppressor Function by Interacting with p53-EZH2 Pathway in Gastric Cancer

Fu, Hualin; Ma, Yue; Lu, Lungen; Hou, Peng; Li, Baojie; Jin, Weilin; Cui, Daxiang

doi:10.1166/jbn.2014.1861

Cited by 63 publications

(61 citation statements)

References 45 publications

(50 reference statements)

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“…Meanwhile, histone methylase EZH2 had no significant expression dynamic, which revealed TET1 had no direct regulation with EZH2. As an oncogene, EZH2 presented high expression level in cancer cells through activation of MEK-ERK pathway to increase the amount of H3K27me355. The low and stable level of EZH2 also demonstrated mTet1 modified dairy goat mGSCs did not concerate as oncogene and tumor suppressor are altering or replacing each other56, it kept normal with stable self-renewal and proliferative ability.…”

Section: Discussionmentioning

confidence: 96%

The Modification of Tet1 in Male Germline Stem Cells and Interact with PCNA, HDAC1 to promote their Self-renewal and Proliferation

Zheng

Zhai

et al. 2016

Sci Rep

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Epigenetic modification plays key roles in spermatogenesis, especially DNA methylation dynamic is important in sustaining normal spermatogenesis. Ten-eleven translocation 1 (Tet1) is not only a key demethylase, which works in specific gene regions, but also crosstalks with partners to regulate epigenetic progress as protein complexes. Dairy goat is an important livestock in China, while the unstable culture system in vitro inhibits optimization of new dairy goat species. The study of epigenetic modification in male germline stem cells (mGSCs) is beneficial to the optimization of adult stem cell culture system in vitro, and the improvement of sperm quality and breeding of selected livestock. In our study, we not only analyzed the morphology, gene expression, DNA methylation and histone methylation dynamic in mouse Tet1 (mTet1) modified mGSCs, we also analyzed the stemness ability by in vivo transplantation and explored the functional mechanism of Tet1 in dairy goat mGSCs. The results showed mTet1 modified mGSCs had better self-renewal and proliferation ability than wild-type mGSCs, mTet1 could also up-regulate JMJD3 to decrease H3K27me3, which also showed to suppress the MEK-ERK pathway. Furthermore, Co-IP analysis demonstrated that TET1 interact with PCNA and HDAC1 by forming protein complexes to comprehensively regulate dairy goat mGSCs and spermatogenesis.

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Section: Discussionmentioning

confidence: 96%

The Modification of Tet1 in Male Germline Stem Cells and Interact with PCNA, HDAC1 to promote their Self-renewal and Proliferation

Zheng

Zhai

et al. 2016

Sci Rep

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“…It further verified the disturbance of DNA methylation in cancer [74]. Consistently, Fu et al showed that TET1 functioned as tumor suppressor via TSGs activation and oncogenes inhibition [75]. Herein, 5hmC dysregulation due to disturbance of various TETs indicates that any TET is probably involved in demethylation of GC.…”

Section: Demethylation Via 5hmc Conversion In Cancermentioning

confidence: 68%

Physiological and pathological implications of 5-hydroxymethylcytosine in diseases

et al. 2016

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Gene expression is the prerequisite of proteins. Diverse stimuli result in alteration of gene expression profile by base substitution for quite a long time. However, during the past decades, accumulating studies proved that bases modification is involved in this process. CpG islands (CGIs) are DNA fragments enriched in CpG repeats which mostly locate in promoters. They are frequently modified, methylated in most conditions, thereby suggesting a role of methylation in profiling gene expression. DNA methylation occurs in many conditions, such as cancer, embryogenesis, nervous system diseases etc. Recently, 5-hydroxymethylcytosine (5hmC), the product of 5-methylcytosine (5mC) demethylation, is emerging as a novel demethylation marker in many disorders. Consistently, conversion of 5mC to 5hmC has been proved in many studies. Here, we reviewed recent studies concerning demethylation via 5hmC conversion in several conditions and progress of therapeutics-associated with it in clinic. We aimed to unveil its physiological and pathological significance in diseases and to provide insight into its clinical application potential.

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“…TET1 has tumor suppressive activity in colon, breast, and gastric cancers (Fu et al, 2014; Lu et al, 2014; Neri et al, 2015; Sun et al, 2013). Here, we show that TET1 expression in lung cancer and GBM cells inhibits tumor formation, indicating that TET1 confers tumor suppressive activity in lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells

et al. 2016

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SUMMARY Oncogene-induced DNA methylation-mediated transcriptional silencing of tumor suppressors frequently occurs in cancer, but the mechanism and functional role of this silencing in oncogenesis is not fully understood. Here, we show that oncogenic epidermal growth factor receptor (EGFR) induces silencing of multiple unrelated tumor suppressors in lung adenocarcinomas and glioblastomas by inhibiting the DNA demethylase TET oncogene family member 1 (TET1) via the C/EBPα transcription factor. After oncogenic EGFR inhibition, TET1 binds to tumor suppressor promoters and induces their re-expression through active DNA demethylation. Ectopic expression of TET1 potently inhibits lung and glioblastoma tumor growth, and TET1 knockdown confers resistance to EGFR inhibitors in lung cancer cells. Lung cancer samples exhibited reduced TET1 expression or TET1 cytoplasmic localization in the majority of cases. Collectively, these results identify a conserved pathway of oncogenic EGFR-induced DNA methylation-mediated transcriptional silencing of tumor suppressors, which may have therapeutic benefit for oncogenic EGFR-mediated lung cancers and glioblastomas.

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TET1 Exerts Its Tumor Suppressor Function by Interacting with p53-EZH2 Pathway in Gastric Cancer

Cited by 63 publications

References 45 publications

The Modification of Tet1 in Male Germline Stem Cells and Interact with PCNA, HDAC1 to promote their Self-renewal and Proliferation

The Modification of Tet1 in Male Germline Stem Cells and Interact with PCNA, HDAC1 to promote their Self-renewal and Proliferation

Physiological and pathological implications of 5-hydroxymethylcytosine in diseases

Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells

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