scholarly journals Correction: Novel Role of NOX in Supporting Aerobic Glycolysis in Cancer Cells with Mitochondrial Dysfunction and as a Potential Target for Cancer Therapy

PLoS Biology ◽  
2017 ◽  
Vol 15 (12) ◽  
pp. e1002616 ◽  
Author(s):  
Weiqin Lu ◽  
Yumin Hu ◽  
Gang Chen ◽  
Zhao Chen ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Aerobic Glycolysis ◽  
Potential Target

scholarly journals Novel Role of NOX in Supporting Aerobic Glycolysis in Cancer Cells with Mitochondrial Dysfunction and as a Potential Target for Cancer Therapy

PLoS Biology ◽  
2012 ◽  
Vol 10 (5) ◽  
pp. e1001326 ◽  
Author(s):  
Weiqin Lu ◽  
Yumin Hu ◽  
Gang Chen ◽  
Zhao Chen ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Aerobic Glycolysis ◽  
Potential Target

Relevance of mitochondrial dysfunction during Sorafenib-induced cell death in liver cancer cells. Role of oxidative and nitrogen reactive species

2021 ◽  
Vol 165 ◽  
pp. 54
Author(s):  
Patricia de la Cruz-Ojeda ◽  
M. Ángeles Rodríguez-Hernández ◽  
Elena Navarro-Villarán ◽  
Paloma Gallego ◽  
Pavla Staňková ◽  
...  
Keyword(s):  
Cell Death ◽  
Liver Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Reactive Species ◽  
Liver Cancer Cells ◽  
Nitrogen Reactive Species

Magneto Mitochondrial Dysfunction Mediated Cancer Cell Death Using Intracellular Magnetic Nano-Transducers

2021 ◽  
Author(s):  
Wooram Park ◽  
Seok-Jo Kim ◽  
Paul Cheresh ◽  
Jeanho Yun ◽  
Byeongdu Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Cancer Cell ◽  
High Sensitivity ◽  
Intrinsic Pathway ◽  
Cancer Cell Death

Mitochondria are crucial regulators of the intrinsic pathway of cancer cell death. The high sensitivity of cancer cells to mitochondrial dysfunction offers opportunities for emerging targets in cancer therapy. Herein,...

The F1Fo-ATPase inhibitor, IF1, is a critical regulator of energy metabolism in cancer cells

2021 ◽  
Vol 49 (2) ◽  
pp. 815-827
Author(s):  
Giancarlo Solaini ◽  
Gianluca Sgarbi ◽  
Alessandra Baracca
Keyword(s):  
Cancer Cells ◽  
Atp Synthase ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Metabolic Reprogramming ◽  
Endogenous Inhibitor ◽  
Atpase Inhibitor ◽  
Molecular Action ◽  
F1fo Atpase

In the last two decades, IF1, the endogenous inhibitor of the mitochondrial F1Fo-ATPase (ATP synthase) has assumed greater and ever greater interest since it has been found to be overexpressed in many cancers. At present, several findings indicate that IF1 is capable of playing a central role in cancer cells by promoting metabolic reprogramming, proliferation and resistance to cell death. However, the mechanism(s) at the basis of this pro-oncogenic action of IF1 remains elusive. Here, we recall the main features of the mechanism of the action of IF1 when the ATP synthase works in reverse, and discuss the experimental evidence that support its relevance in cancer cells. In particular, a clear pro-oncogenic action of IF1 is to avoid wasting of ATP when cancer cells are exposed to anoxia or near anoxia conditions, therefore favoring cell survival and tumor growth. However, more recently, various papers have described IF1 as an inhibitor of the ATP synthase when it is working physiologically (i.e. synthethizing ATP), and therefore reprogramming cell metabolism to aerobic glycolysis. In contrast, other studies excluded IF1 as an inhibitor of ATP synthase under normoxia, providing the basis for a hot debate. This review focuses on the role of IF1 as a modulator of the ATP synthase in normoxic cancer cells with the awareness that the knowledge of the molecular action of IF1 on the ATP synthase is crucial in unravelling the molecular mechanism(s) responsible for the pro-oncogenic role of IF1 in cancer and in developing related anticancer strategies.

scholarly journals Mitochondrial Metabolism in PDAC: From Better Knowledge to New Targeting Strategies

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 270 ◽  
Author(s):  
Gabriela Reyes-Castellanos ◽  
Rawand Masoud ◽  
Alice Carrier
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Mitochondrial Metabolism ◽  
Metabolic Reprogramming ◽  
Ductal Adenocarcinoma ◽  
Current View ◽  
Pancreatic Cancer Cells

Cancer cells reprogram their metabolism to meet bioenergetics and biosynthetic demands. The first observation of metabolic reprogramming in cancer cells was made a century ago (“Warburg effect” or aerobic glycolysis), leading to the classical view that cancer metabolism relies on a glycolytic phenotype. There is now accumulating evidence that most cancers also rely on mitochondria to satisfy their metabolic needs. Indeed, the current view of cancer metabolism places mitochondria as key actors in all facets of cancer progression. Importantly, mitochondrial metabolism has become a very promising target in cancer therapy, including for refractory cancers such as Pancreatic Ductal AdenoCarcinoma (PDAC). In particular, mitochondrial oxidative phosphorylation (OXPHOS) is an important target in cancer therapy. Other therapeutic strategies include the targeting of glutamine and fatty acids metabolism, as well as the inhibition of the TriCarboxylic Acid (TCA) cycle intermediates. A better knowledge of how pancreatic cancer cells regulate mitochondrial metabolism will allow the identification of metabolic vulnerabilities and thus novel and more efficient therapeutic options for the benefit of each patient.

scholarly journals Vacuolar H+-ATPase Subunit V0C Regulates Aerobic Glycolysis of Esophageal Cancer Cells via PKM2 Signaling

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1137 ◽  
Author(s):  
Sung Wook Son ◽  
Gia Cac Chau ◽  
Seong-Tae Kim ◽  
Sung Hee Um
Keyword(s):  
Esophageal Cancer ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Aerobic Glycolysis ◽  
Glycolytic Enzyme ◽  
Ph Homeostasis ◽  
Atpase Subunit ◽  
Esophageal Cancer Cells

The vacuolar H+-adenosine triphosphatase (ATPase) subunit V0C (ATP6V0C), a proton-conducting, pore-forming subunit of vacuolar ATPase, maintains pH homeostasis and induces organelle acidification. The intracellular and extracellular pH of cancer cells affects their growth; however, the role of ATP6V0C in highly invasive esophageal cancer cells (ECCs) remains unclear. In this study, we examined the role of ATP6V0C in glucose metabolism in ECCs. The ATP6V0C depletion attenuated ECC proliferation, invasion, and suppressed glucose metabolism, as indicated by reduced glucose uptake and decreased lactate and adenosine triphosphate (ATP) production in cells. Consistent with this, expression of glycolytic enzyme and the extracellular acidification rate (ECAR) were also decreased by ATP6V0C knockdown. Mechanistically, ATP6V0C interacted with pyruvate kinase isoform M2 (PKM2), a key regulator of glycolysis in ECCs. The ATP6V0C depletion reduced PKM2 phosphorylation at tyrosine residue 105 (Tyr105), leading to inhibition of nuclear translocation of PKM2. In addition, ATP6V0C was recruited at hypoxia response element (HRE) sites in the lactate dehydrogenase A (LDHA) gene for glycolysis. Thus, our data suggest that ATP6V0C enhances aerobic glycolysis and motility in ECCs.

scholarly journals MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 29 ◽  
Author(s):  
Hyun Ah Seo ◽  
Sokviseth Moeng ◽  
Seokmin Sim ◽  
Hyo Jeong Kuh ◽  
Soo Young Choi ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Resistance ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Different Types ◽  
Therapeutic Responses

The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.

scholarly journals Target Misfolded Protein Clearance Pathway for Cancer Therapy

Proceedings ◽  
2020 ◽  
Vol 40 (1) ◽  
pp. 45
Author(s):  
Apar Pataer
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Prion Proteins ◽  
Misfolded Protein ◽  
Breast Cancer Patients ◽  
Protein Kinase R ◽  
Protein Clearance ◽  
Dependent Protein

The role of RNA-dependent protein kinase R (PKR) and its association with misfolded protein expression in cancer cells are unclear. Herein we report that PKR regulates misfolded protein clearance by preventing it release through exosomes and promoting lysosomal degradation of misfolded prion proteins in cancer cells. We demonstrated that PKR contributes to the lysosome function and regulates misfolded prion protein clearance. We hypothesized that PKR-associated lysosome function is critical for cancer but not normal cell survival, representing an effective approach for highly targeted cancer therapy. In screening a compound library, we identified two PKR-associated compound 1 did not affect normal cells but selectively induced cell death in cancer cells depending on their PKR expression status. Pac 1 significantly inhibited the growth of human lung and breast xenograft tumors in mice with no toxicity. Pac 1 binds to PI4K2A and disrupts the PKR/PI4K2A associated lysosome complex, contributing to destabilization of cancer cell lysosomes and triggering cell death. We observed that PKR and PI4K2A play significant prognostic roles in breast cancer patients. These results demonstrate that targeting of a PI4K2A/PKR lysosome complex may be an effective approach for cancer therapy.

scholarly journals The expanded role of fatty acid metabolism in cancer: new aspects and targets

2019 ◽  
Vol 2 (3) ◽  
pp. 183-191 ◽  
Author(s):  
Ming Chen ◽  
Jiaoti Huang
Keyword(s):  
Fatty Acids ◽  
Cell Proliferation ◽  
Lipid Metabolism ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Acid Metabolism ◽  
Metabolic Reprogramming ◽  
Metabolic Plasticity ◽  
Support Cell

Abstract Cancer cells undergo metabolic reprogramming to support cell proliferation, growth, and dissemination. Alterations in lipid metabolism, and specifically the uptake and synthesis of fatty acids (FAs), comprise one well-documented aspect of this reprogramming. Recent studies have revealed an expanded range of roles played by FA in promoting the aggressiveness of cancer while simultaneously identifying new potential targets for cancer therapy. This article provides a brief review of these advances in our understanding of FA metabolism in cancer, highlighting both recent discoveries and the inherent challenges caused by the metabolic plasticity of cancer cells in targeting lipid metabolism for cancer therapy.

scholarly journals Therapeutic targeting of the PI4K2A/PKR lysosome network is critical for misfolded protein clearance and survival in cancer cells

Oncogene ◽  
2019 ◽  
Vol 39 (4) ◽  
pp. 801-813 ◽  
Author(s):  
Apar Pataer ◽  
Bulent Ozpolat ◽  
RuPing Shao ◽  
Neil R. Cashman ◽  
Steven S. Plotkin ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Prion Proteins ◽  
Misfolded Protein ◽  
Breast Cancer Patients ◽  
Protein Kinase R ◽  
Protein Clearance ◽  
Dependent Protein

Abstract The role of RNA-dependent protein kinase R (PKR) and its association with misfolded protein expression in cancer cells are unclear. Herein we report that PKR regulates misfolded protein clearance by preventing it release through exosomes and promoting lysosomal degradation of misfolded prion proteins in cancer cells. We demonstrated that PKR contributes to the lysosome function and regulates misfolded prion protein clearance. We hypothesized that PKR-associated lysosome function is critical for cancer but not normal cell survival, representing an effective approach for highly targeted cancer therapy. In screening a compound library, we identified two PKR-associated compounds 1 and 2 (Pac 1 and 2) did not affect normal cells but selectively induced cell death in cancer cells depending on their PKR expression status. Pac 1 significantly inhibited the growth of human lung and breast xenograft tumors in mice with no toxicity. Pac 1 binds to PI4K2A and disrupts the PKR/PI4K2A-associated lysosome complex, contributing to destabilization of cancer cell lysosomes and triggering cell death. We observed that PKR and PI4K2A play significant prognostic roles in breast cancer patients. These results demonstrate that targeting of a PI4K2A/PKR lysosome complex may be an effective approach for cancer therapy.

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