The H3K9 Methyltransferase G9a Represses E-cadherin and is Associated with Myometrial Invasion in Endometrial Cancer

Hsiao, Sheng Mou; Chen, Luyang; Chen, Chi-An; Chien, Ming Hsien; Hua, Kuo Tai; Hsiao, Michael; Kuo, Min Liang; Lin, Wei

doi:10.1245/s10434-015-4379-5

Cited by 32 publications

(25 citation statements)

References 39 publications

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“…The epigenetic modification of histones can govern the stability of the EMT plasticity. Methylation of histone H3 on lysine 9 (H3K9me2) was reported to mediate E-cadherin transcriptional repression and drive tumor invasion and metastasis in endometrial cancer [ 89 ]. The histone H3 Lysine 9 methyltransferase, G9a, was also critical for Snail-mediated E-cadherin repression in human breast cancer [ 90 , 91 ].…”

Section: Molecular Mechanisms Of Emtmentioning

confidence: 99%

Epithelial-Mesenchymal Transition and Breast Cancer

Sarkissyan

Vadgama

2016

JCM

168

128

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Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT) in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs) and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges.

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Section: Molecular Mechanisms Of Emtmentioning

confidence: 99%

Epithelial-Mesenchymal Transition and Breast Cancer

Sarkissyan

Vadgama

2016

JCM

168

128

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“…(6) The similar effect can be observed in case of irreversible epigenetic silencing of the CDH1 gene. (7) In fact, these mechanisms can be also implicated in carcinogenesis associated with the irreversible EMT.…”

Section: See Article On Page 934mentioning

confidence: 99%

“…In addition, mutations in the cadherin 1 ( CDH1 ) gene and the absence of E‐cadherin or production of its altered variant may provoke a cascade of molecular events that lead to permanent activation of EMT transcription factors and maintenance of the mesenchymal phenotype . The similar effect can be observed in case of irreversible epigenetic silencing of the CDH1 gene . In fact, these mechanisms can be also implicated in carcinogenesis associated with the irreversible EMT.…”

mentioning

confidence: 99%

A fixed partial epithelial‐mesenchymal transition (EMT) triggers carcinogenesis, whereas asymmetrical division of hybrid EMT cells drives cancer progression

Denisov

Перельмутер

2018

Hepatology

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“…Among the HMTs, G9a, involved in embryonic development [ 21 ], was considered to maintain the stemness property in this study. G9a mainly methylates on histone 3 lysine 9 (H3K9) to regulate the transcriptional genes through gene silencing [ 22 ]. G9a can maintain CSC characteristics in head and neck squamous cell carcinoma [ 23 ]; therefore, we investigated whether G9a is generated as the downstream protein of EGFR in EGFR-positive lung tumor cells, for determining the stemness property in EGFR-positive lung cancer.…”

Section: Introductionmentioning

confidence: 99%

YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells

et al. 2017

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Cancer stem cell survival is the leading factor for tumor recurrence after tumor-suppressive treatments. Therefore, specific and efficient inhibitors of cancer stemness must be discovered for reducing tumor recurrence. YM155 has been indicated to significantly reduce stemness-derived tumorsphere formation. However, the pharmaceutical mechanism of YM155 against cancer stemness is unclear. This study investigated the potential mechanism of YM155 against cancer stemness in lung cancer. Tumorspheres derived from epidermal growth factor receptor (EGFR)-mutant HCC827 and EGFR wild-type A549 cells expressing higher cancer stemness markers (CD133, Oct4, and Nanog) were used as cancer stemness models. We observed that EGFR autophosphorylation (Y1068) was higher in HCC827- and A549-derived tumorspheres than in parental cells; this autophosphorylation induced tumorsphere formation by activating G9a-mediated stemness. Notably, YM155 inhibited tumorsphere formation by blocking the autophosphorylation of EGFR and the EGFR-G9a-mediated stemness pathway. The chemical and genetic inhibition of EGFR and G9a revealed the significant role of the EGFR-G9a pathway in maintaining the cancer stemness property. In conclusion, this study not only revealed that EGFR could trigger tumorsphere formation by elevating G9a-mediated stemness but also demonstrated that YM155 could inhibit this formation by simultaneously blocking EGFR autophosphorylation and G9a activity, thus acting as a potent agent against lung cancer stemness.

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The H3K9 Methyltransferase G9a Represses E-cadherin and is Associated with Myometrial Invasion in Endometrial Cancer

Cited by 32 publications

References 39 publications

Epithelial-Mesenchymal Transition and Breast Cancer

Epithelial-Mesenchymal Transition and Breast Cancer

A fixed partial epithelial‐mesenchymal transition (EMT) triggers carcinogenesis, whereas asymmetrical division of hybrid EMT cells drives cancer progression

YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells

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