Introducing Molecular Biology of Head and Neck Cancer
John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford in Head & Neck Surgery Plastic Surgery, 2018
As long ago as the 1920s Otto Warburg performed experiments on tumours aimed at determining the metabolic processes used by cells in the tumour, which revealed high levels of glycolysis (‘fermentation’) as well as respiration typical of normal tissues.192 However, it was not until the 1950s that more quantitative experiments revealed that tumour cells generate much of their energy from fermentation (i.e. glycolysis) whereas normal cells typically use mostly respiration.193 This observation has been put to good use in PET-CT using the increased capacity of tumour to uptake a radioactive glucose analogue to image tumours.194 It seems extraordinary, but it is only in the last decade or so that cancer biology has begun to focus in earnest on the so-called Warburg effect, namely the tendency for cancer cells to obtain substantial amounts of energy from aerobic glycolysis. This effect is so ubiquitous that many are now trying to take advantage of this phenomenon for therapeutic purposes. Many of the genes found altered in head and neck cancers have been implicated in metabolic alterations in cancer cells, chief amongst these being TP53,195MYC196 and PIK3CA,197 all of which have been shown in vitro to modulate cancer metabolic profiles. In the case of TP53, studies have already identified potential strategies for therapeutic interventions.198
Mitochondrial Dysfunction, Immune Systems, Their Diseases, and Possible Treatments
Shamim I. Ahmad in Handbook of Mitochondrial Dysfunction, 2019
While it is not clear whether changes in mitochondrial dynamics are a cause or a consequence of the process, it is well known that tumor cells rewire their energy metabolism towards glycolysis and increase their glucose uptake. This phenomenon, known as the Warburg effect, is thought to provide tumor cells with survival and proliferative advantages.44 This switch in tumor cell metabolism also impact immune cells from the tumor microenvironment. For instance, tumor-derived lactic acid generating by glycolysis triggers the polarization of tumor associated macrophages (TAM). Indeed, lactic acid acts as a signalling molecule which induces a M2-phenotype in TAMS in an HIF1-α -dependent manner, characterized by immunosuppressive and tumor-promoting functions.45
Analysis Of Volatile Organic Compounds For Cancer Diagnosis
Raquel Cumeras, Xavier Correig in Volatile organic compound analysis in biomedical diagnosis applications, 2018
In the metabolism of glucose by mammalian cells, energy is harnessed in the form of ATP through the oxidation of its carbon bonds, producing lactate as the end product or, upon full oxidation of glucose through oxidative phosphorylation in the mitochondria, CO2 (Liberti and Locasale, 2016). However, in tumor cells, the rate of glucose metabolism increases and lactate is produced even in the presence of oxygen and fully functioning mitochondria (aerobic glycolysis) (Liberti and Locasale, 2016). The change in the metabolism of glucose in cancer cells favoring glycolysis to oxidative phosphorylation even in the presence of oxygen is known as Warburg effect (Warburg, 1956) and is characterized by an increased glucose consumption and lactate production. The increased levels of lactate production lead to the cancer cell microenvironment and tissue to become acidic. This acidic environment permits breakage of the basement membrane and allows accessibility of cancer cells to blood vessels, which could lead to the development of metastases through blood (Gatenby and Gillies, 2004). Therefore, it could be hypothesized that these changes in cancer cells metabolism, when compared to non-malignant cells, could lead to the release of VOCs in breath linked to cancer.
Improving therapeutic resistance: beginning with targeting the tumor microenvironment
Published in Journal of Chemotherapy, 2022
Xiao-ying Guan, Xiao-li Guan, Zuo-yi Jiao
Although the Warburg effect is a hallmark of cancer, it has been gradually discovered that some cancers rely on oxidative phosphorylation (OXPHOS) to produce cellular energy rather than aerobic glycolysis, and the concept of the reverse Warburg effect was proposed. The reverse Warburg effect is a two-compartment model to illustrate the metabolic coupling between stromal cells or CAFs and cancer cells. CAFs undergo aerobic glycolysis to generate pyruvate and lactic acid, which in turn supply OXPHOS to tumor cells to efficiently produce ATP [73]. The transport of lactic acid from cancer cells and the extracellular space is facilitated by lactic acid transporters called monocarboxylic acid transporters. Lactic acid, produced under either anoxic or aerobic conditions, acts as the primary metabolic fuel of cancer cells [74].
Obesity, Inflammation, and Advanced Prostate Cancer
Published in Nutrition and Cancer, 2021
Armando Olivas, Ramona Salcedo Price
TNFα exposure, even at low doses, has also proven sufficient to induce deregulation of cellular energetics, another hallmark of cancer (121). Low dose exposure (10 ng/mL) of TNFα for 48 h, sufficed to induce glycolytic ATP production while concomitantly suppressing oxidative phosphorylation in pre-cancerous and PCa cell lines despite aerobic conditions (121). Interestingly, the shift in cellular energetics observed was also accompanied by lactate production across all cell lines, these distinctive features are indicative of a phenomenon termed the “Warburg effect”. The Warburg effect is a characteristic typical of cancerous cells that is proposed to confer cancer cells survival advantages including a greater rate of ATP synthesis, increased glucose uptake to provide carbon atoms for anabolic processes, and acidification of the microenvironment which facilitates migration and invasiveness (122).
Role of macrophage in nanomedicine-based disease treatment
Published in Drug Delivery, 2021
Siwei Song, Hui Xia, Mengfei Guo, Sufei Wang, Shujing Zhang, Pei Ma, Yang Jin
M1 macrophages exhibit a unique metabolic characteristic called the Warburg effect and also known as aerobic glycolysis (Regdon et al., 2019). Warburg effect is a distinctive form of cellular metabolisms with high levels of glucose uptake and increased conversion of glucose to lactose in the glycolytic pathway. Among these, induced production of iNOS and H2O2 drives the repolarization of macrophages (Orihuela et al., 2016). Inspired by these findings, Tang et al. developed modified zeolitic imidazolate framework-8 (ZIF-8) NPs loaded with s-methylisothiourea hemisulfate salt (SMT) for gas regulation and metabolic reprogramming of synovial macrophages in OA (Zhou et al., 2020). Moreover, Chen, Liu et al. constructed photothermal-triggered NO nanogenerators NO-Hb@siRNA@PLGA-PEG (NHsPP) by assembling photothermal agents and NO molecules within NPs. The combination of various kinds of nanomaterials may thus compensate for individual defects and this practice is now becoming mainstream.
Related Knowledge Centers
- Fermentation
- Lactic Acid Fermentation
- Oxidative Phosphorylation
- Catabolism
- Citric Acid Cycle
- Glycolysis
- Mitochondrion
- Cytosol
- Ethanol Fermentation
- Adenosine Triphosphate