Cancer's Molecular Sweet Tooth and the Warburg Effect

Kim, Jung-whan; Dang, Chi V.

doi:10.1158/0008-5472.can-06-1501

Cited by 1,065 publications

(881 citation statements)

References 20 publications

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“…10 Mitochondria is now considered as a rational target for cancer therapy. 11 Although there is a possibility that atpenins modulate tumor-stromal cell interactions by inhibiting mitochondrial functions, the elucidation of the precise mechanism of action needs to be studied further. We are now studying the effects of atpenins on tumor growth in vivo using mouse xenograft models.…”

Section: Discussionmentioning

confidence: 99%

New atpenins, NBRI23477 A and B, inhibit the growth of human prostate cancer cells

et al. 2009

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The growth and metastasis of prostate cancer are regulated by prostate stroma through the tumor-stromal cell interactions. Small molecules that modulate the tumor-stromal cell interactions will be new anticancer drugs. In the course of our screening of the modulators, we isolated two new atpenins, NBRI23477 A (4) and B (5), from the fermentation broth of Penicillium atramentosum PF1420. Compounds 4 and 5 as well as atpenin A4 (1), A5 (2) and B (3) inhibited the growth of human prostate cancer DU-145 cells in the coculture with human prostate stromal cells more strongly than that of DU-145 cells alone.

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Section: Discussionmentioning

confidence: 99%

New atpenins, NBRI23477 A and B, inhibit the growth of human prostate cancer cells

et al. 2009

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“…The view of cancer as a metabolic disease was gradually displaced with the view of cancer as a genetic disease. While there is renewed interest in the energy metabolism of cancer cells, it is widely thought that the Warburg effect and the metabolic defects expressed in cancer cells arise primarily from genomic mutability selected during tumor progression [36][37][38][39]. Emerging evidence, however, questions the genetic origin of cancer and suggests that cancer is primarily a metabolic disease.…”

Section: Introductionmentioning

confidence: 99%

Cancer as a Metabolic Disease

Seyfried¹

2012

188

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Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention.

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“…In contrast, cancer cells depend mostly on glycolysis, the aerobic breakdown of glucose into the energy-storing molecule adenosine triphosphate (ATP). This altered energy dependency is known as the 'Warburg effect' and is a hallmark of cancer cells (Warburg, 1956;Kim and Dang, 2006;Chen et al, 2007;Gatenby and Gillies, 2007;DeBerardinis et al, 2008;Gillies et al, 2008;Hsu and Sabatini, 2008;Kroemer and Pouyssegur, 2008).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of lactate dehydrogenase A by ErbB2 through heat shock factor 1 promotes breast cancer cell glycolysis and growth

et al. 2009

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ErbB2 has been shown to activate signaling molecules that may regulate glucose metabolism. However, there is no evidence reported to directly link ErbB2 to glycolysis, and the mechanism underlying ErbB2-enhanced glycolysis is poorly understood. In this study, we investigated the role and mechanism of ErbB2 in regulating glycolysis. We found that ErbB2-overexpressing cells possessed a significantly higher level of glycolysis when compared to the ErbB2-low-expressing cells, and the downregulation of ErbB2 markedly decreased glycolysis. Overexpression of ErbB2 increased the expression of glycolysis-regulating molecules lactate dehydrogenase A (LDH-A) and heat shock factor 1 (HSF1). ErbB2 activated HSF1, indicated by the increased HSF1 trimer formation, and promoted HSF1 protein synthesis. HSF1 bound to LDH-A promoter and the downregulation of HSF1 reduced the expression of LDH-A and subsequently decreased cancer cell glycolysis and growth. Moreover, the glycolysis inhibitors, 2-deoxyglucose and oxamate, selectively inhibited the growth of ErbB2-overexpressing cells. Taken together, this study shows that in human breast cancer cells, ErbB2 promotes glycolysis at least partially through the HSF1-mediated upregulation of LDH-A. This pathway may have a major role in regulating glucose metabolism in breast cancer cells. These novel findings have important implications for the design of new approaches to target ErbB2-overexpressing breast cancers.

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Cancer's Molecular Sweet Tooth and the Warburg Effect

Cited by 1,065 publications

References 20 publications

New atpenins, NBRI23477 A and B, inhibit the growth of human prostate cancer cells

New atpenins, NBRI23477 A and B, inhibit the growth of human prostate cancer cells

Cancer as a Metabolic Disease

Upregulation of lactate dehydrogenase A by ErbB2 through heat shock factor 1 promotes breast cancer cell glycolysis and growth

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