Cancer Metabolism: Molecular Insights of Cancer through Metabolomics

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Cell Metabolism".

Deadline for manuscript submissions: closed (15 April 2023) | Viewed by 6418

Special Issue Editors


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Guest Editor
Proteomics Lab, National Centre for Cell Science (NCCS), Ganeshkhind, SPPU Campus, Pune 411007, India
Interests: cancer biomarkers; proteomics; metabolomics; mass spectrometry

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Guest Editor
Amrita School of Nanosciences and Molecular Medicine (ASNSMM), Amrita Vishwa Vidyapeetham, Kochi 682041, Kerala, India
Interests: metabolomics; proteomics; cancer; mass spectrometry; pharmacology

Special Issue Information

Dear Colleagues,

Cancer is a multifaceted process that involves alterations at gene and various micro and macro molecular levels. The dysregulation of metabolism in cancer is now well-appreciated and therefore, ‘Re-programming energy metabolism’ has been recognized as one of the hallmarks in cancer development in modern cancer biology. Moreover, understanding the complete metabolic alterations in cancer helps to develop novel predictive biomarkers and therapeutic targets as well as mechanisms towards arresting metastasis and drug resistance for better future cancer management strategies.   Therefore, understanding cancer metabolism is crucial for a better understanding of cancer biology and for the discovery of novel metabolite biomarkers for cancer diagnosis. The aim of the present Special Issue is to collect original articles and reviews that focus on diverse aspects of cancer metabolism as well as studies that aim to discover novel metabolite(s) as cancer biomarkers. The issue will explore the mechanisms of metabolic reprograming associated with cancer and how it drives cancer progression, metastasis and drug resistance. Unravelling the regulatory roles of the cancer metabolites will support the development of novel diagnostics and therapeutic approaches for cancer.

Dr. Srikanth Rapole
Dr. Bhargab Kalita
Guest Editors

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Keywords

  • cancer
  • metabolic reprograming
  • metabolite biomarkers
  • omics technologies
  • cancer metabolites
  • tumor metabolism
  • metastasis
  • drug resistance
  • metabolomics

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Published Papers (3 papers)

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Research

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11 pages, 2366 KiB  
Article
Nuclear PTEN Regulates Thymidylate Biosynthesis in Human Prostate Cancer Cell Lines
by Zoe N. Loh, Mu-En Wang, Changxin Wan, John M. Asara, Zhicheng Ji and Ming Chen
Metabolites 2023, 13(8), 939; https://doi.org/10.3390/metabo13080939 - 11 Aug 2023
Viewed by 1713
Abstract
The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor governs a variety of biological processes, including metabolism, by acting on distinct molecular targets in different subcellular compartments. In the cytosol, inactive PTEN can be recruited to the plasma membrane where [...] Read more.
The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor governs a variety of biological processes, including metabolism, by acting on distinct molecular targets in different subcellular compartments. In the cytosol, inactive PTEN can be recruited to the plasma membrane where it dimerizes and functions as a lipid phosphatase to regulate metabolic processes mediated by the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway. However, the metabolic regulation of PTEN in the nucleus remains undefined. Here, using a gain-of-function approach to targeting PTEN to the plasma membrane and nucleus, we show that nuclear PTEN contributes to pyrimidine metabolism, in particular de novo thymidylate (dTMP) biosynthesis. PTEN appears to regulate dTMP biosynthesis through interaction with methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), a key enzyme that generates 5,10-methylenetetrahydrofolate, a cofactor required for thymidylate synthase (TYMS) to catalyze deoxyuridylate (dUMP) into dTMP. Our findings reveal a nuclear function for PTEN in controlling dTMP biosynthesis and may also have implications for targeting nuclear-excluded PTEN prostate cancer cells with antifolate drugs. Full article
(This article belongs to the Special Issue Cancer Metabolism: Molecular Insights of Cancer through Metabolomics)
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29 pages, 2552 KiB  
Article
Differential Inhibition of Anaplerotic Pyruvate Carboxylation and Glutaminolysis-Fueled Anabolism Underlies Distinct Toxicity of Selenium Agents in Human Lung Cancer
by Teresa W.-M. Fan, Jason Winnike, Ahmad Al-Attar, Alexander C. Belshoff, Pawel K. Lorkiewicz, Jin Lian Tan, Min Wu, Richard M. Higashi and Andrew N. Lane
Metabolites 2023, 13(7), 774; https://doi.org/10.3390/metabo13070774 - 21 Jun 2023
Cited by 1 | Viewed by 1570
Abstract
Past chemopreventive human trials on dietary selenium supplements produced controversial outcomes. They largely employed selenomethionine (SeM)-based diets. SeM was less toxic than selenite or methylseleninic acid (MSeA) to lung cancer cells. We thus investigated the toxic action of these Se agents in two [...] Read more.
Past chemopreventive human trials on dietary selenium supplements produced controversial outcomes. They largely employed selenomethionine (SeM)-based diets. SeM was less toxic than selenite or methylseleninic acid (MSeA) to lung cancer cells. We thus investigated the toxic action of these Se agents in two non-small cell lung cancer (NSCLC) cell lines and ex vivo organotypic cultures (OTC) of NSCLC patient lung tissues. Stable isotope-resolved metabolomics (SIRM) using 13C6-glucose and 13C5,15N2-glutamine tracers with gene knockdowns were employed to examine metabolic dysregulations associated with cell type- and treatment-dependent phenotypic changes. Inhibition of key anaplerotic processes, pyruvate carboxylation (PyC) and glutaminolysis were elicited by exposure to MSeA and selenite but not by SeM. They were accompanied by distinct anabolic dysregulation and reflected cell type-dependent changes in proliferation/death/cell cycle arrest. NSCLC OTC showed similar responses of PyC and/or glutaminolysis to the three agents, which correlated with tissue damages. Altogether, we found differential perturbations in anaplerosis-fueled anabolic pathways to underlie the distinct anti-cancer actions of the three Se agents, which could also explain the failure of SeM-based chemoprevention trials. Full article
(This article belongs to the Special Issue Cancer Metabolism: Molecular Insights of Cancer through Metabolomics)
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Review

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14 pages, 489 KiB  
Review
Reprogramming of Cellular Metabolism and Its Therapeutic Applications in Thyroid Cancer
by Yuji Nagayama and Koichiro Hamada
Metabolites 2022, 12(12), 1214; https://doi.org/10.3390/metabo12121214 - 3 Dec 2022
Cited by 8 | Viewed by 2594
Abstract
Metabolism is a series of life-sustaining chemical reactions in organisms, providing energy required for cellular processes and building blocks for cellular constituents of proteins, lipids, carbohydrates and nucleic acids. Cancer cells frequently reprogram their metabolic behaviors to adapt their rapid proliferation and altered [...] Read more.
Metabolism is a series of life-sustaining chemical reactions in organisms, providing energy required for cellular processes and building blocks for cellular constituents of proteins, lipids, carbohydrates and nucleic acids. Cancer cells frequently reprogram their metabolic behaviors to adapt their rapid proliferation and altered tumor microenvironments. Not only aerobic glycolysis (also termed the Warburg effect) but also altered mitochondrial metabolism, amino acid metabolism and lipid metabolism play important roles for cancer growth and aggressiveness. Thus, the mechanistic elucidation of these metabolic changes is invaluable for understanding the pathogenesis of cancers and developing novel metabolism-targeted therapies. In this review article, we first provide an overview of essential metabolic mechanisms, and then summarize the recent findings of metabolic reprogramming and the recent reports of metabolism-targeted therapies for thyroid cancer. Full article
(This article belongs to the Special Issue Cancer Metabolism: Molecular Insights of Cancer through Metabolomics)
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