scholarly journals The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Chang Liu ◽  
Ying Jin ◽  
Zhimin Fan
Keyword(s):  
Overall Survival ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Cancer Patients ◽  
Warburg Effect ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Glycolysis Process ◽  
New Molecular Targets ◽  
The Warburg Effect

Although chemotherapy can improve the overall survival and prognosis of cancer patients, chemoresistance remains an obstacle due to the diversity, heterogeneity, and adaptability to environmental alters in clinic. To determine more possibilities for cancer therapy, recent studies have begun to explore changes in the metabolism, especially glycolysis. The Warburg effect is a hallmark of cancer that refers to the preference of cancer cells to metabolize glucose anaerobically rather than aerobically, even under normoxia, which contributes to chemoresistance. However, the association between glycolysis and chemoresistance and molecular mechanisms of glycolysis-induced chemoresistance remains unclear. This review describes the mechanism of glycolysis-induced chemoresistance from the aspects of glycolysis process, signaling pathways, tumor microenvironment, and their interactions. The understanding of how glycolysis induces chemoresistance may provide new molecular targets and concepts for cancer therapy.

scholarly journals Valproic acid Suppresses Breast Cancer Cell Growth Through Triggering Pyruvate Kinase M2 Isoform Mediated Warburg Effect

2021 ◽  
Vol 30 ◽  
pp. 096368972110275
Author(s):  
Zhen Li ◽  
Lina Yang ◽  
Shuai Zhang ◽  
Jiaqi Song ◽  
Huanran Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Valproic Acid ◽  
Cancer Therapy ◽  
Pyruvate Kinase ◽  
Histone Deacetylases ◽  
Warburg Effect ◽  
Broad Class ◽  
Pyruvate Kinase M2 ◽  
Breast Cancer Cell Growth ◽  
The Warburg Effect

Energy metabolism programming is a hallmark of cancer, and serves as a potent target of cancer therapy. Valproic acid (VPA), a broad Class I histone deacetylases (HDACs) inhibitor, has been used as a therapeutic agent for cancer. However, the detail mechanism about the potential role of VPA on the Warburg effect in breast cancer remains unclear. In this study, we highlight that VPA significantly attenuates the Warburg effect by decreasing the expression of pyruvate kinase M2 isoform (PKM2), leading to inhibited cell proliferation and reduced colony formation in breast cancer MCF-7 and MDA-MB-231 cells. Mechanistically, Warburg effect suppression triggered by VPA was mediated by inactivation of ERK1/2 phosphorylation through reduced HDAC1 expression, resulting in suppressing breast cancer growth. In summary, we uncover a novel mechanism of VPA in regulating the Warburg effect which is essential for developing the effective approach in breast cancer therapy.

scholarly journals The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5557
Author(s):  
Alexandre Vallée ◽  
Yves Lecarpentier ◽  
Jean-Noël Vallée
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Warburg Effect ◽  
Target Genes ◽  
Glucose Transporter ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Metabolic Reprogramming ◽  
Pyruvate Dehydrogenase Kinase ◽  
The Warburg Effect

The canonical WNT/β-catenin pathway is upregulated in cancers and plays a major role in proliferation, invasion, apoptosis and angiogenesis. Nuclear β-catenin accumulation is associated with cancer. Hypoxic mechanisms lead to the activation of the hypoxia-inducible factor (HIF)-1α, promoting glycolytic and energetic metabolism and angiogenesis. However, HIF-1α is degraded by the HIF prolyl hydroxylase under normoxia, conditions under which the WNT/β-catenin pathway can activate HIF-1α. This review is therefore focused on the interaction between the upregulated WNT/β-catenin pathway and the metabolic processes underlying cancer mechanisms under normoxic conditions. The WNT pathway stimulates the PI3K/Akt pathway, the STAT3 pathway and the transduction of WNT/β-catenin target genes (such as c-Myc) to activate HIF-1α activity in a hypoxia-independent manner. In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. The activation of the Wnt/β-catenin pathway induces gene transactivation via WNT target genes, c-Myc and cyclin D1, or via HIF-1α. This in turn encodes aerobic glycolysis enzymes, including glucose transporter, hexokinase 2, pyruvate kinase M2, pyruvate dehydrogenase kinase 1 and lactate dehydrogenase-A, leading to lactate production. The increase in lactate production is associated with modifications to the tumor microenvironment and tumor growth under normoxic conditions. Moreover, increased lactate production is associated with overexpression of VEGF, a key inducer of angiogenesis. Thus, under normoxic conditions, overstimulation of the WNT/β-catenin pathway leads to modifications of the tumor microenvironment and activation of the Warburg effect, autophagy and glutaminolysis, which in turn participate in tumor growth.

scholarly journals Surmounting Chemotherapy and Radioresistance in Chondrosarcoma: Molecular Mechanisms and Therapeutic Targets

Sarcoma ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Anne C. Onishi ◽  
Alexander M. Hincker ◽  
Francis Y. Lee
Keyword(s):  
Surgical Resection ◽  
Successful Treatment ◽  
Radiation Resistance ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Molecular Targets ◽  
Curative Treatment ◽  
Primary Malignancy ◽  
Future Direction ◽  
New Molecular Targets

Chondrosarcoma, a primary malignancy of bone, has eluded successful treatment with modern chemotherapeutic and radiation regimens. To date, surgical resection of these tumors remains the only curative treatment offered to patients with this diagnosis. Understanding and exploring the nature of chemotherapy and radiation resistance in chondrosarcoma could lead to new molecular targets and more directed therapy for these notoriously difficult-to-treat tumors. Here we review the most current hypotheses regarding the molecular mechanisms mediating chemotherapy and radiation resistance and the future direction of chondrosarcoma therapy research.

scholarly journals The effect of certain autophagy proteins (LC3b and Beclin) and apotosis (Casp8 and Bcl-2) on the clinical course of ovarian cancer

2021 ◽  
Vol 67 (4) ◽  
pp. 474-479
Author(s):  
Aliia Gafiullina ◽  
Zinaida Afanaseva ◽  
Karim Garipov ◽  
Zinaida Abramova
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Drug Therapy ◽  
Molecular Mechanisms ◽  
Clinical Course ◽  
Molecular Targets ◽  
Cochrane Library ◽  
Search For Information ◽  
New Molecular Targets

Treatment of ovarian cancer remains an important problem in practical oncology due to the increase in morbidity and mortality from this disease. The aim is to summarize the available literature data on the molecular mechanisms of the participation of various proteins of autophagy and apoptosis in the development, progression, formation of chemoresistance and in the assessment of the prognosis of epithelial ovarian cancer. Materials and methods. The search for information was carried out in the materials of the databases Medline, Cochrane Library, Elibrary, NCBI, RSCI, instructions for the medical use of drugs, using keywords in the title. Used 39 articles to write this systematic review. Results. The review examines the molecular mechanisms of autophagy and apoptosis involved in the progression of ovarian cancer and in the formation of resistance to anticancer drug therapy. It has been shown that modulation of autophagy and apoptosis can change the effectiveness of drug treatment for this tumor. Conclusion. Considering the literature data on the ambiguous role of autophagy and apoptosis in the course of ovarian cancer and the formation of resistance to antitumor treatment, further study is required and the search for new molecular targets for their modulation is required.

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