Warburg Effect or Reverse Warburg Effect? A Review of Cancer Metabolism

Xu, Xiao Dong; Shao, Shi Xiu; Jiang, Hai Ping; Cao, Yan; Wang, Yong Hua; Yang, Xue; Wang, You Lin; Wang, Xinsheng; Niu, Hai

doi:10.1159/000375435

Cited by 166 publications

(142 citation statements)

References 38 publications

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“…These results indicate that miR-125b-induced deregulation of glucose metabolism is not a typical Warburg effect. However, metabolic plasticity and metabolic heterogeneity have been found in some cancers with aggressive phenotype [40–46]. It also has been reported that aerobic glycolysis is less active in T-ALL cells than normal T cells.…”

Section: Discussionmentioning

confidence: 99%

miR-125b regulates differentiation and metabolic reprogramming of T cell acute lymphoblastic leukemia by directly targeting A20

et al. 2016

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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy. Although it has been reported that overexpression of miR-125b leads to T-ALL development, the underlying mechanisms of miR-125b action are still unclear. The goal of this study is to delineate the role of miR-125b in T-ALL development. We found that miR-125b is highly expressed in undifferentiated leukemic T cells (CD4-negative) while its expression is low in differentiated T cells (CD4-positive). Overexpression of miR-125b increased the CD4-negative population in T cells, whereas depletion of miR-125b by miR-125b-sponge decreased the CD4-negative cell population. We identified that A20 (TNFAIP3) is a direct target of miR-125b in T cells. Overexpression of miR-125b also increased glucose uptake and oxygen consumption in T cells through targeting A20. Furthermore, restoration of A20 in miR-125b-overexpressing cells decreased the CD4-negative population in T cell leukemia, and decreased glucose uptake and oxygen consumption to the basal level of T cells transfected with vector. In conclusion, our data demonstrate that miR-125b regulates differentiation and reprogramming of T cell glucose metabolism via targeting A20. Since both de-differentiation and dysregulated glucose metabolism contribute to the development of T-cell leukemia, these findings provide novel insights into the understanding and treatment of T-ALL.

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Section: Discussionmentioning

confidence: 99%

miR-125b regulates differentiation and metabolic reprogramming of T cell acute lymphoblastic leukemia by directly targeting A20

et al. 2016

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“…Over the past couple of decades, advances in technology have allowed mitochondrial function to be studied in a far greater detail, and it is now realised that cancer cells have active and functional mitochondria, contrary to Warburg's theory [13,14]. In the last decade, research has shown that different tumour types (and indeed subpopulations within a tumour) have different bioenergetic alterations.…”

Section: The Warburg Effectmentioning

confidence: 99%

The Warburg effect: 80 years on

Potter

Newport

Morten

2016

Biochemical Society Transactions

371

341

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Influential research by Warburg and Cori in the 1920s ignited interest in how cancer cells' energy generation is different from that of normal cells. They observed high glucose consumption and large amounts of lactate excretion from cancer cells compared with normal cells, which oxidised glucose using mitochondria. It was therefore assumed that cancer cells were generating energy using glycolysis rather than mitochondrial oxidative phosphorylation, and that the mitochondria were dysfunctional. Advances in research techniques since then have shown the mitochondria in cancer cells to be functional across a range of tumour types. However, different tumour populations have different bioenergetic alterations in order to meet their high energy requirement; the Warburg effect is not consistent across all cancer types. This review will discuss the metabolic reprogramming of cancer, possible explanations for the high glucose consumption in cancer cells observed by Warburg, and suggest key experimental practices we should consider when studying the metabolism of cancer.

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“…Mechanistically, LDHA depletion results in downregulation of p21 and Bax, and upregulation of cyclin D and Bcl2, which contributes to growth arrest; moreover, si-LDHA results in MMPs downregulation, facilitating blockage of cell migration and invasion in vitro. Therefore, our findings demonstrated that LDHA, an oncogene contributed to the Warburg effect [8,14] , had a drastic implication on tumor development and progression in renal cancer.…”

Section: Discussionmentioning

confidence: 73%

“…The Warburg effect, also known as aerobic glycolysis [8] , is a hallmark of tumor cell metabolism [8][9][10][11][12] , which is described by the increased glucose uptake and the lactate production in tumor cells even under normal oxygen concentrations. Until recently, the important function of aerobic glycolysis in tumor development has been widespread and palpably recognized [13] .…”

mentioning

confidence: 99%

Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma

Wang

et al. 2016

Urol Int

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Purpose: Lactate dehydrogenase A (LDHA), which functions as a crucial enzyme in transforming from pyruvate into lactate, has been reported to be overexpressed in various advanced cancer and its silencing has turned out to be tumor suppressive. Previous studies have showed that the expression of LDHA was higher in renal cell carcinoma (RCC) than that in corresponding normal renal tissue. However, the function of LDHA in RCC, and its possible mechanism in tumor progression, has not been investigated. Methods: MTT and cell cycle assay were performed to explore the growth of the renal cells. Transwell assay for the migration and invasion and tube formation were conducted to detect the metastatic properties of the renal cancer. Results: Here, we show that siRNA-mediated knockdown of LDHA inhibits cell proliferation by decreasing cell cycle and promoting apoptosis in renal cancer cell lines. Mechanistically, LDHA siRNA treatment altered the expression of cell cycle- and apoptosis-related proteins, including p21, cyclin D1, Bcl-2 and Bax. In addition, LDHA siRNA treatment leads to markedly diminished migratory and invasive ability by reducing the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Conclusions: These findings are consistent with the view that LDHA, as an oncogene, might be a potential therapeutic target in RCC.

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Warburg Effect or Reverse Warburg Effect? A Review of Cancer Metabolism

Cited by 166 publications

References 38 publications

miR-125b regulates differentiation and metabolic reprogramming of T cell acute lymphoblastic leukemia by directly targeting A20

miR-125b regulates differentiation and metabolic reprogramming of T cell acute lymphoblastic leukemia by directly targeting A20

The Warburg effect: 80 years on

Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma

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