Targeting Metabolic Reprogramming as an Anti- Cancer Strategy: Aiming at Monocarboxylate Transporters

Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.

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The Development of Single-Cell Metabolism and Its Role in Studying Cancer Emergent Properties

Frontiers in Oncology ◽

10.3389/fonc.2021.814085 ◽

2022 ◽

Vol 11 ◽

Author(s):

Dingju Wei ◽

Meng Xu ◽

Zhihua Wang ◽

Jingjing Tong

Keyword(s):

Tumor Cell ◽

Single Cell ◽

Immune Escape ◽

Cell Metabolism ◽

Single Cells ◽

Metabolic Reprogramming ◽

Biological Information ◽

Emergent Properties ◽

Anti Cancer ◽

Cell Metabolomics

Metabolic reprogramming is one of the hallmarks of malignant tumors, which provides energy and material basis for tumor rapid proliferation, immune escape, as well as extensive invasion and metastasis. Blocking the energy and material supply of tumor cells is one of the strategies to treat tumor, however tumor cell metabolic heterogeneity prevents metabolic-based anti-cancer treatment. Therefore, searching for the key metabolic factors that regulate cell cancerous change and tumor recurrence has become a major challenge. Emerging technology––single-cell metabolomics is different from the traditional metabolomics that obtains average information of a group of cells. Single-cell metabolomics identifies the metabolites of single cells in different states by mass spectrometry, and captures the molecular biological information of the energy and substances synthesized in single cells, which provides more detailed information for tumor treatment metabolic target screening. This review will combine the current research status of tumor cell metabolism with the advantages of single-cell metabolomics technology, and explore the role of single-cell sequencing technology in searching key factors regulating tumor metabolism. The addition of single-cell technology will accelerate the development of metabolism-based anti-cancer strategies, which may greatly improve the prognostic survival rate of cancer patients.

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Targeting T cell metabolism in the tumor microenvironment: an anti-cancer therapeutic strategy

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1409-3 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 18

Author(s):

Zhongping Yin ◽

Ling Bai ◽

Wei Li ◽

Tanlun Zeng ◽

Huimin Tian ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Tumor Microenvironment ◽

Metabolic Pathways ◽

Cell Metabolism ◽

Basic Research ◽

Metabolic Reprogramming ◽

Activated T Cells ◽

Cell Functions ◽

Anti Cancer

Abstract T cells play important roles in anti-tumor immunity. Emerging evidence has revealed that distinct metabolic changes impact the activation and differentiation of T cells. Tailoring immune responses by manipulating cellular metabolic pathways and the identification of new targets may provide new options for cancer immunotherapy. In this review, we focus on recent advances in the metabolic reprogramming of different subtypes of T cells and T cell functions. We summarize how metabolic pathways accurately regulate T cell development, differentiation, and function in the tumor microenvironment. Because of the similar metabolism in activated T cells and tumor cells, we also describe the effect of the tumor microenvironment on T cell metabolism reprogramming, which may provide strategies for maximal anti-cancer effects and enhancing the immunity of T cells. Thus, studies of T lymphocyte metabolism can not only facilitate the basic research of immune metabolism, but also provide potential targets for drug development and new strategies for clinical treatment of cancer.

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Wnt Signaling in Cancer Metabolism and Immunity

Cancers ◽

10.3390/cancers11070904 ◽

2019 ◽

Vol 11 (7) ◽

pp. 904 ◽

Cited By ~ 23

Author(s):

Sara El-Sahli ◽

Ying Xie ◽

Lisheng Wang ◽

Sheng Liu

Keyword(s):

Wnt Signaling ◽

Cancer Cells ◽

Cancer Metabolism ◽

Metabolic Reprogramming ◽

Tumor Initiating Cells ◽

Tumor Plasticity ◽

Anti Cancer ◽

Wnt Ligands ◽

Canonical Wnt

The Wingless (Wnt)/β-catenin pathway has long been associated with tumorigenesis, tumor plasticity, and tumor-initiating cells called cancer stem cells (CSCs). Wnt signaling has recently been implicated in the metabolic reprogramming of cancer cells. Aberrant Wnt signaling is considered to be a driver of metabolic alterations of glycolysis, glutaminolysis, and lipogenesis, processes essential to the survival of bulk and CSC populations. Over the past decade, the Wnt pathway has also been shown to regulate the tumor microenvironment (TME) and anti-cancer immunity. Wnt ligands released by tumor cells in the TME facilitate the immune evasion of cancer cells and hamper immunotherapy. In this review, we illustrate the role of the canonical Wnt/β-catenin pathway in cancer metabolism and immunity to explore the potential therapeutic approach of targeting Wnt signaling from a metabolic and immunological perspective.

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Cancer-specific Therapeutic Potential of Resveratrol: Metabolic Approach against Hallmarks of Cancer

Functional Foods in Health and Disease ◽

10.31989/ffhd.v3i8.44 ◽

2013 ◽

Vol 3 (8) ◽

pp. 332 ◽

Cited By ~ 3

Author(s):

Dong Hoon Suh ◽

Mi-Kyung Kim ◽

Hee Seung Kim ◽

Hyun Hoon Chung ◽

Yong Sang Song

Keyword(s):

Cancer Cells ◽

Therapeutic Potential ◽

Metabolic Reprogramming ◽

Metabolic Demand ◽

Macromolecular Synthesis ◽

Invasion And Metastasis ◽

Hallmarks Of Cancer ◽

Cancer Hallmarks ◽

Tissue Invasion ◽

Anti Cancer

Cancer hallmarks include evading apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion and metastasis. Cancer cells undergo metabolic reprogramming and inevitably take advantage of glycolysis to meet the increased metabolic demand: rapid energy generation and macromolecular synthesis. Resveratrol, a polyphenolic phytoalexin, is known to exhibit pleiotropic anti-cancer effects most of which are linked to metabolic reprogramming in cancer cells. This review summarizes various anti-cancer effects of resveratrol in the context of cancer hallmarks in relation to metabolic reprogramming.

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Immunity Depletion, Telomere Imbalance, and Cancer-associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Caloric Restriction

10.1101/2021.03.10.433216 ◽

2021 ◽

Author(s):

Evan Maestri ◽

Kalina Duszka ◽

Vladimir A Kuznetsov

Keyword(s):

Gene Expression ◽

Cancer Biology ◽

Cell Activation ◽

Expression Profiles ◽

Specific Treatment ◽

Metabolic Reprogramming ◽

Telomere Maintenance ◽

Systematic Analysis ◽

Therapeutic Benefits ◽

Anti Cancer

AbstractSystematic analysis of calorie restriction (CR) mechanisms and pathways in cancer biology has not been carried out, leaving therapeutic benefits unclear. Using a systems biology approach and metadata analysis, we studied gene expression changes in the response of normal mouse duodenum mucosa (DM) to short-term (2-weeks) 25% CR as a biological model. We found a high similarity of gene expression profiles in human and mouse DM tissues. Surprisingly, 26% of the 467 CR responding differential expressed genes (DEGs) in mice consist of cancer-associated genes—most never studied in CR contexts. The DEGs were enriched with over-expressed cell cycle, oncogenes, and metabolic reprogramming pathways (MRP) that determine tissue-specific tumorigenesis, cancer, and stem cell activation; tumor suppressors and apoptosis genes were under-expressed. DEG enrichments suggest a misbalance in telomere maintenance and activation of metabolic pathways playing dual (anti-cancer and pro-oncogenic) roles. Immune system genes (ISGs) consist of 37% of the total DEGs; the majority of ISGs are suppressed, including cell-autonomous immunity and tumor immune evasion controls. Thus, CR induces MRP suppressing multiple immune mechanics and activating oncogenic pathways, potentially driving pre-malignant and cancer states. These findings change the paradigm regarding the anti-cancer role of CR and may initiate specific treatment target development.

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Immune-mediated anti-tumor effects of metformin; targeting metabolic reprogramming of T cells as a new possible mechanism for anti-cancer effects of metformin

Biochemical Pharmacology ◽

10.1016/j.bcp.2019.113787 ◽

2020 ◽

Vol 174 ◽

pp. 113787 ◽

Cited By ~ 8

Author(s):

Saman Bahrambeigi ◽

Vahid Shafiei-Irannejad

Keyword(s):

T Cells ◽

Metabolic Reprogramming ◽

Immune Mediated ◽

Anti Cancer

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Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms20163960 ◽

2019 ◽

Vol 20 (16) ◽

pp. 3960 ◽

Cited By ~ 1

Author(s):

Yi-Ta Hsieh ◽

Yi-Fen Chen ◽

Shu-Chun Lin ◽

Kuo-Wei Chang ◽

Wan-Chun Li

Keyword(s):

Head And Neck ◽

Metabolic Pathways ◽

Cancer Metabolism ◽

Molecular Level ◽

Review Article ◽

Metabolic Reprogramming ◽

Prognostic Indicators ◽

Normal Cells ◽

Anti Cancer ◽

Great Energy

Considering the great energy and biomass demand for cell survival, cancer cells exhibit unique metabolic signatures compared to normal cells. Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent neoplasms worldwide. Recent findings have shown that environmental challenges, as well as intrinsic metabolic manipulations, could modulate HNSCC experimentally and serve as clinic prognostic indicators, suggesting that a better understanding of dynamic metabolic changes during HNSCC development could be of great benefit for developing adjuvant anti-cancer schemes other than conventional therapies. However, the following questions are still poorly understood: (i) how does metabolic reprogramming occur during HNSCC development? (ii) how does the tumorous milieu contribute to HNSCC tumourigenesis? and (iii) at the molecular level, how do various metabolic cues interact with each other to control the oncogenicity and therapeutic sensitivity of HNSCC? In this review article, the regulatory roles of different metabolic pathways in HNSCC and its microenvironment in controlling the malignancy are therefore discussed in the hope of providing a systemic overview regarding what we knew and how cancer metabolism could be translated for the development of anti-cancer therapeutic reagents.

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