Glucose Metabolism in Breast Cancer and its Implication in Cancer Therapy

Li, Ning; Tan, Wenhao; Li, Jing; Li, Ping; Lee, Simon; Wang, Ying; Gong, Yuewen

doi:10.4236/ijcm.2011.22022

Cited by 14 publications

(14 citation statements)

References 167 publications

(222 reference statements)

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“…In breast cancer cells, overexpression of trans-membrane glucose transporters (GLUT) facilitate the rapid and higher rates of glucose uptake to support the increased rates of glycolysis (Fig. 3C) [123,144]. In 3D cultures of ER-ve/HER2+ve human mammary epithelial cells (HMECs) lapatinib (an FDA approved dual tyrosine kinase inhibitor for EGFR and HER2 receptor tyrosine kinases) treatment associated inhibition of HER2/Akt signaling led to the downregulation of GLUT4, reduction in glucose uptake and inhibition of aerobic glycolysis in HER2-overexpressing cells resulting in decreased proliferation and increased apoptosis of these cells [124].…”

Section: Aberrant Glucose Metabolismmentioning

confidence: 99%

“…In an MMTV-neu mouse model, administration of low-doses of lapatinib, during the early stages of mammary gland transformation, caused effective inhibition of HER2/ Akt signaling and downregulation of GLUT4 which was linked to significantly delayed mammary tumor initiation and progression and extended tumor-free survival [124]. In malignant breast cancer tissue, the activity of key glycolytic enzymes, hexokinase (HK), phosphofructokinase (PFK), aldolase (ALDO) and pyruvate kinase (PK) are significantly higher when compared to normal or benign breast tumors [144]. Overexpression of HK in breast tumors is also associated with suppression of apoptosis [144].…”

Section: Aberrant Glucose Metabolismmentioning

confidence: 99%

“…In malignant breast cancer tissue, the activity of key glycolytic enzymes, hexokinase (HK), phosphofructokinase (PFK), aldolase (ALDO) and pyruvate kinase (PK) are significantly higher when compared to normal or benign breast tumors [144]. Overexpression of HK in breast tumors is also associated with suppression of apoptosis [144]. Higher expression levels of lactate dehydrogenase A (LDH-A) was observed in breast cancer tissue and was associated with invasiveness and hence is considered as marker for tumor progression [144].…”

Section: Aberrant Glucose Metabolismmentioning

confidence: 99%

“…Overexpression of HK in breast tumors is also associated with suppression of apoptosis [144]. Higher expression levels of lactate dehydrogenase A (LDH-A) was observed in breast cancer tissue and was associated with invasiveness and hence is considered as marker for tumor progression [144]. ROS mediated overexpression and nutrient depletion and hypoxia associated stabilization of the transcription factor HIF1 further drives glycolysis by supporting the overexpression of glucose transporters and enzymes associated with aerobic glycolysis such as HK and LDH [144].…”

Section: Aberrant Glucose Metabolismmentioning

confidence: 99%

“…Higher expression levels of lactate dehydrogenase A (LDH-A) was observed in breast cancer tissue and was associated with invasiveness and hence is considered as marker for tumor progression [144]. ROS mediated overexpression and nutrient depletion and hypoxia associated stabilization of the transcription factor HIF1 further drives glycolysis by supporting the overexpression of glucose transporters and enzymes associated with aerobic glycolysis such as HK and LDH [144]. HIF1 mediated activation of pyruvate dehydrogenase kinase 1 (PDK1) followed by PDK1 mediated phosphorylation and subsequent inhibition of pyruvate dehydrogenase (PDH) activity restricts the conversion of pyruvate to acetyl-CoA consequently shifting the metabolic flux to generate lactate [144][145][146].…”

Section: Aberrant Glucose Metabolismmentioning

confidence: 99%

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Challenges and perspectives in the treatment of diabetes associated breast cancer

Samuel

Varghese

et al. 2018

Cancer Treatment Reviews

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Type 2 diabetes mellitus is one of the most common chronic disease worldwide and affects all cross-sections of the society including children, women, youth and adults. Scientific evidence has linked diabetes to higher incidence, accelerated progression and increased aggressiveness of different cancers. Among the different forms of cancer, research has reinforced a link between diabetes and the risk of breast cancer. Some studies have specifically linked diabetes to the highly aggressive, triple negative breast cancers (TNBCs) which do not respond to conventional hormonal/HER2 targeted interventions, have chances of early recurrence, metastasize, tend to be more invasive in nature and develop drug resistance. Commonly used anti-diabetic drugs, such as metformin, have recently gained importance in the treatment of breast cancer due to their proposed anti-cancer properties. Here we discuss the link between diabetes and breast cancer, the metabolic disturbances in diabetes that support the development of breast cancer, the challenges involved and future perspective and directions. We link the three main metabolic disturbances (dyslipidemia, hyperinsulinemia and hyperglycemia) that occur in diabetes to potential aberrant molecular pathways that may lead to the development of an oncogenic phenotype of the breast tissue, thereby leading to acceleration of cell growth, proliferation, migration, inflammation, angiogenesis, EMT and metastasis and inhibition of apoptosis in breast cancer cells. Furthermore, managing diabetes and treating cancer using a combination of anti-diabetic and classical anti-cancer drugs should prove to be more efficient in the treatment diabetes associated cancers.

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Section: Aberrant Glucose Metabolismmentioning

confidence: 99%

Section: Aberrant Glucose Metabolismmentioning

confidence: 99%

Section: Aberrant Glucose Metabolismmentioning

confidence: 99%

Section: Aberrant Glucose Metabolismmentioning

confidence: 99%

Section: Aberrant Glucose Metabolismmentioning

confidence: 99%

See 3 more Smart Citations

Challenges and perspectives in the treatment of diabetes associated breast cancer

Samuel

Varghese

et al. 2018

Cancer Treatment Reviews

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Glucose metabolism and lncRNAs in breast cancer: Sworn friend

Wang

et al. 2022

Cancer Medicine

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Background: Glucose metabolism disorder is a common feature in cancer.Cancer cells generate much energy through anaerobic glycolysis, which promote the development of tumors. However, long non-coding RNA may play an important role in this process. Our aim is to explore a prognostic risk model based on the glucose metabolism-related lncRNAs which provides clues that lncRNAs predict a clinical outcome through glucose metabolism in breast cancer.Methods: 1222 RNA-seq were extracted from the TCGA database, and 74 glucose metabolism-related genes were loaded from the GSEA website. Then, 7 glucose metabolism-related lncRNAs risk score model was developed by univariate, Lasso, and multivariate regression analysis. The lncRNA risk model showed that highrisk patients predict a poor clinical outcome with high reliability (P=2.838×10-6).Univariate and multivariate independent prognostic analysis and ROC curve analysis proved that the risk score was an independent prognostic factor in breast cancer with an AUC value of 0.652. Finally, Gene set enrichment analysis showed that cell cycle-related pathways were significantly enriched in a high-risk group. Results: Our results showed that glucose metabolism-related lncRNAs can affect breast cancer progression. 7 glucose metabolism-related lncRNAs prognostic signature was established to evaluate the OS of patients with breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors and expressed highly in the high-risk group. A Nomogram was made based on this signature to judge patients' living conditions and prognosis. Conclusion: 7 glucose metabolism-related lncRNAs risk score model had a high prognostic value in breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors. AP001505.1 expression was increased in most triple-negative breast cancer cells treated with high glucose, which may also take part in breast cancer progression and potential therapeutic targets K E Y W O R D S breast cancer, glucose metabolism, lncRNA, lncRNA risk model

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Potential survival markers in cancer patients undergoing chemotherapy

Roszkowski

Filipiak²,

Wiśniewska³

et al. 2014

Clin Exp Med

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Due to the importance of the identification of chemotherapy outcome prognostic factors, we attempted to establish the potential of oxidative stress/DNA damage parameters such as prognostic markers. The aim of the study was to determine whether platinum derivative-based chemotherapy in cancer patients (n = 66) is responsible for systemic oxidatively damaged DNA and whether damage biomarkers, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and the modified base 8-oxo-7,8-dihydroguanine (8-oxo-Gua), in urine and DNA may be used as a prognostic factor for the outcome of chemotherapy. All the aforementioned modifications were analyzed using techniques involving high-performance liquid chromatography/electrochemical detection (HPLC/EC) or HPLC/gas chromatography-mass spectrometry (GC-MS). Among all the analyzed parameters, the significantly decreased levels of 8-oxo-Gua in urine collected from a subgroup of patients 24 h after the first infusion of the drug, as compared with the baseline levels, correlated with a significantly longer overall survival (OS) (60 months after therapy) than in the subgroup without any decrease of this parameter after therapy (median OS = 24 months, p = 0.007). Moreover, a significantly longer OS was also observed in a group with increased urine levels of 8-oxo-dG after chemotherapy (38.6 vs. 20.5 months, p = 0.03). The results of our study suggest that patients with decreased 8-oxo-Gua levels and increased 8-oxo-dG levels in urine 24 h after the first dose should be considered as better responders to the administered chemotherapy, with a lower risk of death. The conclusion may permit the use of these parameters as markers for predicting the clinical outcome of platinum derivative-based chemotherapy.

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Glucose Metabolism in Breast Cancer and its Implication in Cancer Therapy

Abstract: It is well known that malignant cells have accelerated glucose uptake and metabolism in order to

Cited by 14 publications

References 167 publications

Challenges and perspectives in the treatment of diabetes associated breast cancer

Challenges and perspectives in the treatment of diabetes associated breast cancer

Glucose metabolism and lncRNAs in breast cancer: Sworn friend

Potential survival markers in cancer patients undergoing chemotherapy

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