ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis

Liu, Xue Song; Haines, Jenna E.; Mehanna, Elie; Genet, Matthew; Ben-Sahra, Issam; Asara, John M.; Manning, Brendan D.; Yuan, Zhi Min

doi:10.1101/gad.245910.114

Cited by 98 publications

(107 citation statements)

References 32 publications

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“…The importance of ZBTB7A-mediated suppression of MCAM expression in human melanoma is further supported by data derived from our analysis of a cohort of human melanoma patient samples, which showed a clear inverse correlation of ZBTB7A and MCAM expression in association with melanoma progression. Recently we identified a tumor suppressive function of ZBTB7A by repressing the transcription of glycolysis genes (29). In human colon cancers, we observed significantly reverse correlation between ZBTB7A and glycolysis genes (29), while in melanoma ZBTB7A do not show significant reverse correlation with glycolysis genes, and similarly we do not observe the reverse correlation between ZBTB7A and MCAM in human colon cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Recently we identified a tumor suppressive function of ZBTB7A by repressing the transcription of glycolysis genes (29). In human colon cancers, we observed significantly reverse correlation between ZBTB7A and glycolysis genes (29), while in melanoma ZBTB7A do not show significant reverse correlation with glycolysis genes, and similarly we do not observe the reverse correlation between ZBTB7A and MCAM in human colon cancers. Most importantly depletion of MCAM nearly completely rescued the melanoma metastasis phenotype of ZBTB7A deficient melanoma cells in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

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ZBTB7A Suppresses Melanoma Metastasis by Transcriptionally Repressing MCAM

Liu

Genet

Haines

et al. 2015

Molecular Cancer Research

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The excessive metastatic propensity of melanoma makes it the most deadly form of skin cancer, yet the underlying mechanism of metastasis remains elusive. Here, mining of cancer genome datasets discovered a frequent loss of chromosome 19p13.3 and associated down-regulation of the zinc finger transcription factor ZBTB7A in metastatic melanoma. Functional assessment of ZBTB7A-regulated genes identified MCAM, which encodes an adhesion protein key to melanoma metastasis. Using an integrated approach, it is demonstrated that ZBTB7A directly binds to the promoter and transcriptionally represses the expression of MCAM, establishing ZBTB7A as a bona fide transcriptional repressor of MCAM. Consistently, down-regulation of ZBTB7A results in marked upregulation of MCAM and enhanced melanoma cell invasion and metastasis. An inverse correlation of ZBTB7A and MCAM expression in association with melanoma metastasis is further validated with data from analysis of human melanoma specimens. Implications Together these results uncover a previously unrecognized role of ZBTB7A in negative regulation of melanoma metastasis and have important clinical implications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

ZBTB7A Suppresses Melanoma Metastasis by Transcriptionally Repressing MCAM

Liu

Genet

Haines

et al. 2015

Molecular Cancer Research

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“…ZBTB7A, a member of the POK (POZ/BTB and Krüppel) transcription repressor family, acts as a novel tumor suppressor by directly suppressing glycolysis [88]. ZBTB7A-deficient tumors progress very fast and are extremely sensitive to glycolysis inhibition.…”

Section: Regulation Of Glycolysis In Tumorsmentioning

confidence: 99%

The sweet trap in tumors: aerobic glycolysis and potential targets for therapy

et al. 2016

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Metabolic change is one of the hallmarks of tumor, which has recently attracted a great of attention. One of main metabolic characteristics of tumor cells is the high level of glycolysis even in the presence of oxygen, known as aerobic glycolysis or the Warburg effect. The energy production is much less in glycolysis pathway than that in tricarboxylic acid cycle. The molecular mechanism of a high glycolytic flux in tumor cells remains unclear. A large amount of intermediates derived from glycolytic pathway could meet the biosynthetic requirements of the proliferating cells. Hypoxia-induced HIF-1α, PI3K-Akt-mTOR signaling pathway, and many other factors, such as oncogene activation and tumor suppressor inactivation, drive cancer cells to favor glycolysis over mitochondrial oxidation. Several small molecules targeting glycolytic pathway exhibit promising anticancer activity both in vitro and in vivo. In this review, we will focus on the latest progress in the regulation of aerobic glycolysis and discuss the potential targets for the tumor therapy.

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“…Much of this has been already realized for FOXO, MYC and HIF1a, but other players are likely to emerge. In fact, the ZBTB family of transcription factors has been shown to repress several glycolytic enzymes in fibroblasts and in lymphocytes [40, 41]. It is anticipated that these master regulators will also mediate similar responses in multiple cell types to quickly promote alterations in metabolic pathways that can be solidified by external signaling.…”

Section: Resultsmentioning

confidence: 99%

Cross-talk between signaling and metabolism in the vasculature

Uebelhoer¹,

Iruela‐Arispe²

2016

Vascular Pharmacology

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The link between signaling and metabolism was first recognized with insulin signal transduction. Efficient glucose uptake by the endothelium requires insulin receptor activation to deliver GLUT receptors to the cell surface. More recently however, additional evidence has emerged for a broader crosstalk as signaling events have been shown to regulate a large number of metabolic enzymes. Changes in the metabolic status of endothelial and smooth muscle cells are observed at times of increased proliferative activity and these coincide with activation of cell surface receptors. Intriguingly, a rise in glycolysis appears to be associated with remodeling of the actin cytoskeleton during migration and angiogenesis. Overall, understanding how do signaling and metabolic pathways intersect and cross-regulate each other has become an important question and an emerging cornerstone in vascular biology.

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ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis

Cited by 98 publications

References 32 publications

ZBTB7A Suppresses Melanoma Metastasis by Transcriptionally Repressing MCAM

ZBTB7A Suppresses Melanoma Metastasis by Transcriptionally Repressing MCAM

The sweet trap in tumors: aerobic glycolysis and potential targets for therapy

Cross-talk between signaling and metabolism in the vasculature

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