The Warburg effect and glucose-derived cancer theranostics

Tekade, Rakesh K.; Sun, Xiankai

doi:10.1016/j.drudis.2017.08.003

Cited by 127 publications

(74 citation statements)

References 143 publications

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“…Glycolysis not only provides ATP for tumours, but also changes the surrounding environment of tumours, which provides favourable conditions for the metastasis and invasion of tumours. [ ]…”

Section: Discussionmentioning

confidence: 99%

Kruppel-like factor 2 disturb non-small cell lung cancer energy metabolism by inhibited glutamine consumption

Song

Jin‐Xiang

Tian

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives Metabolic reprogramming is well accepted as a hallmark of cancer. This study aimed to explore the role of Kruppel-like factor 2 (KLF2) in aerobic glycolysis and glutamine consumption of energy metabolism in non-small cell lung cancer (NSCLC) cells. Methods Two different NSCLC cells, A549 and NCI-H1299, were used to investigate the role of KLF2 in glycolysis and glutamine consumption by tracer technique and KLF2 transfection. Key findings The results showed that overexpression KLF could inhibit the energy metabolism and proliferation of NSCLC cells, but had no significant effect on glycolysis reaction and only affected the glutamine consumption of NSCLC cells. In NSCLC cells exposed to glutamine deprivation, the effect of overexpression of KLF2 on cell proliferation and energy metabolism disappeared. It was found that KLF2 could inhibit the expression of glutaminase (GLS) by metabolite tracing technique and so on. However, when GLS inhibitors were given to overexpressing KLF2 NSCLC cells, the intervention effect of KLF2 disappeared. Conclusions Kruppel-like factor 2 could decrease the level of glutamine, participate in the consumption of glutamine by cancer cells, and then inhibit the energy metabolism of cancer cells.

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“…Glycolysis not only provides ATP for tumours, but also changes the surrounding environment of tumours, which provides favourable conditions for the metastasis and invasion of tumours. [ ]…”

Section: Discussionmentioning

confidence: 99%

Kruppel-like factor 2 disturb non-small cell lung cancer energy metabolism by inhibited glutamine consumption

Song

Jin‐Xiang

Tian

et al. 2020

Journal of Pharmacy and Pharmacology

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“…It is generally accepted that by switching the energy source from mitochondrial oxidative phosphorylation to glycolysis, cancer cells gain sufficient biomass-building materials for cell growth and proliferation, and combat highly oxidative microenvironment for better survival 2,3 . This metabolic reprogramming, also known as the Warburg effect, has shown to contribute to tumorigenesis in a variety of cancers, and become a promising target for diagnosis and targeted therapy of cancer 4,5 . However, how cancer cells coordinate glucose metabolism through glycolysis and mitochondrial TCA cycle is largely unknown.…”

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confidence: 99%

O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth

et al. 2020

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Many cancer cells display enhanced glycolysis and suppressed mitochondrial metabolism. This phenomenon, known as the Warburg effect, is critical for tumor development. However, how cancer cells coordinate glucose metabolism through glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle is largely unknown. We demonstrate here that phosphoglycerate kinase 1 (PGK1), the first ATP-producing enzyme in glycolysis, is reversibly and dynamically modified with O-linked N-acetylglucosamine (O-GlcNAc) at threonine 255 (T255). O-GlcNAcylation activates PGK1 activity to enhance lactate production, and simultaneously induces PGK1 translocation into mitochondria. Inside mitochondria, PGK1 acts as a kinase to inhibit pyruvate dehydrogenase (PDH) complex to reduce oxidative phosphorylation. Blocking T255 O-GlcNAcylation of PGK1 decreases colon cancer cell proliferation, suppresses glycolysis, enhances the TCA cycle, and inhibits tumor growth in xenograft models. Furthermore, PGK1 O-GlcNAcylation levels are elevated in human colon cancers. This study highlights O-GlcNAcylation as an important signal for coordinating glycolysis and the TCA cycle to promote tumorigenesis.

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“…The amount of liberated circulating tumor cells (CTCs) from the primary tumor is known to sharply increase during surgery [50]. Thus, the administered carbohydrates may have given such CTCs a systemic biological support from a triple survival benefit through the Warburg effect [12], the insulin /IGF-1 axis [51] and the paracrine signaling with distant located adipocytes [11]. Furthermore, increased IR/IGF signaling promotes the protein synthesis in the same way the PRpathway does.…”

Section: Discussionmentioning

confidence: 99%

Influence of pre-operative oral carbohydrate loading vs. standard fasting procedure on tumor proliferation and clinical outcome in breast cancer patients — a randomized trial

Lende

Austdal

Varhaugvik

et al. 2019

Preprint

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Background The influence of carbohydrates in breast cancer is conflicting.Objective To determine whether preoperative per-oral carbohydrate load influences proliferation in breast tumors.Design Randomized controlled trial.Setting University hospital with primary and secondary care functions in South-West Norway.Patients A population-based cohort of 61 patients with operable breast cancer.Intervention Per-oral carbohydrate load (preOp™) 18 and 2-4 hours before surgery (n=26) or standard pre-operative fasting procedure with free consume of tap water (n=35).Measurements Primary outcome was post-operative tumor proliferation measured as mitotic activity index (MAI). Secondary outcomes were changes in serum insulin, insulin-c-peptide, glucose, IGF-1 and IGFBP3. Other secondary outcomes were patients´ well-being and clinical outcome (median follow-up 88, range 33-97 months).Results In the estrogen receptor (ER) positive subgroup (n=50), high proliferation (MAI≥ 10) occurred more often in the carbohydrate group (CH) than in the fasting group (p=0.038). Progesterone receptor (PR) was more frequently negative in the CH-group (p=0.014). CH-patients had a significant between group rise in insulin (+ 24.31 mIE/L, 95% CI, 15.34 mIE/L to 33.27 mIE/L), insulin c-peptide (+ 1.39 nM, 95% CI, 1.03 nM to 1.77 nM), but reduced IGFBP3 levels (– 0.26 nM; 95% CI, – 0.46 nM to – 0.051 nM). CH-Intervention ER-positive patients had poorer relapse free survival (73%) than the fasting group (100%) (p=0.012; HR= 9.3 (95%CI, 1.1 to 77.7)). In the ER-positive patients, only tumor size (p=0.021; HR=6.07, 95%CI=1.31 to 28.03) and CH-or-fasting grouping (p=0.040; HR=9.30, 95% CI=1.11 to 77.82) had independent prognostic value. The adverse clinical outcome of carbohydrate loading occurred only in T2 patients with Relapse Free Survival of 100% in the fasting group vs. 33% in the CH-group (p=0.015; HR= inf). The CH-group reported less pain on day 5 and 6 compared to the control group (p<0.001) but showed otherwise no factors related to well-being.Limitation Only applicable to ER-positive breast cancer patients with T2-tumors.Conclusions Preoperative carbohydrate load increases proliferation and PR-negativity in ER-positive patients and worsens clinical outcome in ER-positive T2-patients.

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The Warburg effect and glucose-derived cancer theranostics

Cited by 127 publications

References 143 publications

Kruppel-like factor 2 disturb non-small cell lung cancer energy metabolism by inhibited glutamine consumption

Kruppel-like factor 2 disturb non-small cell lung cancer energy metabolism by inhibited glutamine consumption

O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth

Influence of pre-operative oral carbohydrate loading vs. standard fasting procedure on tumor proliferation and clinical outcome in breast cancer patients — a randomized trial

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