Yin Yang 1 Plays an Essential Role in Breast Cancer and Negatively Regulates p27

Wan, Meimei; Huang, Weiwei; Kute, Timothy E.; Miller, Lance D.; Zhang, Qiang; Hatcher, Heather; Wang, Jingxuan; Stovall, Daniel B.; Russell, Gregory B.; Cao, Paul D.; Deng, Zhiyong; Wang, Wei; Zhang, Qingyuan; Lei, Ming; Torti, Suzy V.; Akman, Steven A.; Sui, Guangchao

doi:10.1016/j.ajpath.2012.01.037

Cited by 87 publications

(98 citation statements)

References 66 publications

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“…45), p27 (46), VEGF (33), and others (5,47). Thus, although the whole p53-dependent and -independent mechanisms of YY1 contribution to HIF-1a stabilization and tumorigenesis remains to be elucidated, our results showing that YY1 is associated with HIF-1a regulation under hypoxia further elucidated a novel important role of YY1 in tumor biology, and targeting YY1 might be a potential therapeutic strategy that might give consistent clinical outcomes independent of p53 status in cancer therapy.…”

Section: Discussionmentioning

confidence: 68%

Transcription Factor YY1 Contributes to Tumor Growth by Stabilizing Hypoxia Factor HIF-1α in a p53-Independent Manner

Kasim

Kano

et al. 2013

Cancer Research

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In response to hypoxic stress, hypoxia-inducible factor (HIF)-1a is a critical transcription factor regulating fundamental cellular processes, and its elevated expression level and activity are associated with poor outcomes in most malignancies. The transcription factor Yin Yang 1 (YY1) is an important negative regulator of the tumor suppressor factor p53. However, the role of YY1 under tumor hypoxic condition is poorly understood. Herein, we show that inhibition of YY1 reduced the accumulation of HIF-1a and its activity under hypoxic condition, and consequently downregulated the expression of HIF-1a target genes. Interestingly, our results revealed that the downregulation of HIF-1a by inhibiting YY1 is p53-independent. Functionally, the in vivo experiments revealed that inhibition of YY1 significantly suppressed growth of metastatic cancer cells and lung colonization and also attenuated angiogenesis in a p53-null tumor. Collectively, our findings unraveled a novel mechanism by which YY1 inhibition disrupts hypoxia-stimulated HIF-1a stabilization in a p53-independent manner. Therefore, YY1 inhibition could be considered as a potential tumor therapeutic strategy to give consistent clinical outcomes independent of p53 status. Cancer Res; 73(6);

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Section: Discussionmentioning

confidence: 68%

Transcription Factor YY1 Contributes to Tumor Growth by Stabilizing Hypoxia Factor HIF-1α in a p53-Independent Manner

Kasim

Kano

et al. 2013

Cancer Research

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“…5D-G). Noticeably, the present literatures have pointed to the opposite comprehensions toward the function of YY1 in tumor progression; i.e., YY1 is thought to inhibit cell invasion in breast and lung cancer cells (47), whereas it is found to be overexpressed in breast cancer and can enhance the migration and invasion in nontumorigenic MCF10A mammary cells (48). Apparently, results from this study support the latter viewpoint, as we showed that PRMT7 contributed to the acquisition of migratory and invasive capabilities of breast cancer cells and that PRMT7 directly interacted with YY1 in vitro (Figs.…”

Section: Discussionmentioning

confidence: 99%

PRMT7 Induces Epithelial-to-Mesenchymal Transition and Promotes Metastasis in Breast Cancer

et al. 2014

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Epithelial-to-mesenchymal transition (EMT) enables metastasis. E-cadherin loss is a hallmark of EMT, but there remains an incomplete understanding of the epigenetics of this process. The protein arginine methyltransferase PRMT7 functions in various physiologic processes, including mRNA splicing, DNA repair, and neural differentiation, but its possible roles in cancer and metastasis have not been explored. In this report, we show that PRMT7 is expressed at higher levels in breast carcinoma cells and that elevated PRMT7 mediates EMT and metastasis. PRMT7 could inhibit the expression of E-cadherin by binding to its proximal promoter in a manner associated with altered histone methylation, specifically with elevated H4R3me2s and reduced H3K4me3, H3Ac, and H4Ac, which occurred at the E-cadherin promoter upon EMT induction. Moreover, PRMT7 interacted with YY1 and HDAC3 and was essential to link these proteins to the E-cadherin promoter. Silencing PRMT7 restored E-cadherin expression by repressing H4R3me2s and by increasing H3K4me3 and H4Ac, attenuating cell migration and invasion in MDA-MB-231 breast cancer cells. Overall, our results define PRMT7 as an inducer of breast cancer metastasis and present the opportunity for applying PRMT7-targeted therapeutics to treat highly invasive breast cancers. Cancer Res; 74(19); 5656-67. Ó2014 AACR.

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“…YY1 is suggested to be over-expressed in BC cells and to be a key molecule in BC progression. Knockdown of YY1 led to suppression of the clonogenicity, migration, invasion and tumor formation of BC cells (88).…”

Section: Hdac Inhibitors As Anti-cancer Agentsmentioning

confidence: 99%

Histone Deacetylases as New Therapeutic Targets in Triple-negative Breast Cancer: Progress and Promises

2017

CGP

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Yin Yang 1 Plays an Essential Role in Breast Cancer and Negatively Regulates p27

Cited by 87 publications

References 66 publications

Transcription Factor YY1 Contributes to Tumor Growth by Stabilizing Hypoxia Factor HIF-1α in a p53-Independent Manner

Transcription Factor YY1 Contributes to Tumor Growth by Stabilizing Hypoxia Factor HIF-1α in a p53-Independent Manner

PRMT7 Induces Epithelial-to-Mesenchymal Transition and Promotes Metastasis in Breast Cancer

Histone Deacetylases as New Therapeutic Targets in Triple-negative Breast Cancer: Progress and Promises

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