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Metabolites
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Metabolic Reprogramming: Implications in Cancer, Immune Surveillance and Regenerative Medicine
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Metabolic Reprogramming: Implications in Cancer, Immune Surveillance and Regenerative Medicine

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

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 10393

Special Issue Editors

Prof. Dr. Giuseppe Fiume

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Guest Editor
Department of Experimental and Clinical Medicine, University of Catanzaro “Magna Graecia”, 88100 Catanzaro, Italy
Interests: metabolites profiling of tumor interstitial fluid; immune response; T-lymphocytes; dendritic cells; signal transduction; phagocytosis; antigen presentation; NF-kappaB pathway
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Camillo Palmieri

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Guest Editor
Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Campus Salvatore Venuta-Viale Europa, 88100 Catanzaro, Italy
Interests: clinical biochemistry; leukemia and lymphoma; molecular biomarkers; immunotherapy; T- and B-cell biology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Maurizio Renna

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Guest Editor
Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, Naples, Italy
Interests: endoplasmic reticulum (ER) stress response; analysis of the dynamics of transport in the early secretory pathway; mechanisms regulating autophagosome biogenesis; role of autophagy in neurodegenerative and infectious diseases; role of autophagy in cell growth control and unconventional secretion; pharmacological modulation of autophagy
Special Issues, Collections and Topics in MDPI journals
Prof. Massimo D’Agostino

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Guest Editor
Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, 80131 Naples, Italy
Interests: cell biology; ER stress; mitochondria; cell metabolism

Special Issue Information

Dear Colleagues,

Metabolic reprogramming is a switch in metabolism that cells adopt to support an increased proliferative capacity or to undertake a specific differentiation pathway, and the most paradigmatic examples of these are cancer cells and stem cells, respectively.

Cancer cells show distinct metabolic phenotypes in order to cope with the energetic and metabolic demands required to support tumor growth and progression. Immune cells, including T-lymphocytes, natural killer cells, and macrophages, play a key role in providing broad spectrum protection that serves to eradicate cancerous cells. However, the abnormal metabolic activities of cancer cells influence the nutrient states of the tumor microenvironment (e.g., glucose, glutamine, lactate, and tryptophan-related metabolites such as kynurenine) and limit the antitumoral activity of immune cells. Indeed, tumors escape immunity by inducing metabolic switches in immune cells which lead to immune dysfunction characterized by attenuated tumoricidal effector functions of TILs, such as a minor IFNγ production and cytotoxicity.

Metabolic reprogramming also plays a fundamental role in the regulation of cell fate, and specific metabolic switches occur during the transitions between different pluripotent states as well as during the generation of induced pluripotent stem cells (iPSCs) through somatic reprogramming. Moreover, recent evidence shows that metabolic reprogramming and specific metabolites drive the differentiation pathways of hematopoietic and skeletal muscle tissue stem cells, with fundamental implications for regenerative medicine.

For this Special Issue, we invite research or review articles on metabolic reprogramming of cancer and immune cells as well as stem cells and somatic cells which acquire pluripotency.

Prof. Giuseppe Fiume
Prof. Camillo Palmieri
Prof. Maurizio Renna
Prof. Massimo D’Agostino
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolic reprogramming
  • cancer cell metabolism
  • tumor microenvironment
  • immunometabolism
  • tumor-infiltrating lymphocytes
  • macrophages
  • NK cells
  • exhaustion
  • stem cells
  • pluripotent stem cells
  • induced pluripotent stem cells (iPSCs)

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Published Papers (3 papers)

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Research

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11 pages, 1415 KiB  
Article
Pemetrexed Hinders Translation Inhibition upon Low Glucose in Non-Small Cell Lung Cancer Cells
by Marie Piecyk, Mouna Triki, Pierre-Alexandre Laval, Helena Dragic, Laura Cussonneau, Joelle Fauvre, Cédric Duret, Nicolas Aznar, Toufic Renno, Serge N. Manié, Cédric Chaveroux and Carole Ferraro-Peyret
Metabolites 2021, 11(4), 198; https://doi.org/10.3390/metabo11040198 - 26 Mar 2021
Cited by 3 | Viewed by 2759
Abstract
Genetic alterations in non-small cell lung cancers (NSCLC) stimulate the generation of energy and biomass to promote tumor development. However, the efficacy of the translation process is finely regulated by stress sensors, themselves often controlled by nutrient availability and chemotoxic agents. Yet, the [...] Read more.
Genetic alterations in non-small cell lung cancers (NSCLC) stimulate the generation of energy and biomass to promote tumor development. However, the efficacy of the translation process is finely regulated by stress sensors, themselves often controlled by nutrient availability and chemotoxic agents. Yet, the crosstalk between therapeutic treatment and glucose availability on cell mass generation remains understudied. Herein, we investigated the impact of pemetrexed (PEM) treatment, a first-line agent for NSCLC, on protein synthesis, depending on high or low glucose availability. PEM treatment drastically repressed cell mass and translation when glucose was abundant. Surprisingly, inhibition of protein synthesis caused by low glucose levels was partially dampened upon co-treatment with PEM. Moreover, PEM counteracted the elevation of the endoplasmic reticulum stress (ERS) signal produced upon low glucose availability, providing a molecular explanation for the differential impact of the drug on translation according to glucose levels. Collectively, these data indicate that the ERS constitutes a molecular crosstalk between microenvironmental stressors, contributing to translation reprogramming and proteostasis plasticity. Full article
(This article belongs to the Special Issue Metabolic Reprogramming: Implications in Cancer, Immune Surveillance and Regenerative Medicine)
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20 pages, 702 KiB  
Article
Posttranslational Modifications Pattern in Clear Cell Renal Cell Carcinoma
by Corina Daniela Ene, Mircea Nicolae Penescu, Simona Roxana Georgescu, Mircea Tampa and Ilinca Nicolae
Metabolites 2021, 11(1), 10; https://doi.org/10.3390/metabo11010010 - 27 Dec 2020
Cited by 19 | Viewed by 3168
Abstract
Posttranslational modifications are dynamic enzymatic-mediated processes, regulated in time and space, associated with cancer development. We aimed to evaluate the significance of posttranslational modifications in the pathogenesis of clear cell renal cell carcinoma. The authors developed a prospective, observational study during a period [...] Read more.
Posttranslational modifications are dynamic enzymatic-mediated processes, regulated in time and space, associated with cancer development. We aimed to evaluate the significance of posttranslational modifications in the pathogenesis of clear cell renal cell carcinoma. The authors developed a prospective, observational study during a period of three years and included 55 patients with localized renal cell carcinoma and 30 heathy subjects. Glycosylation, nitration and carbonylation, thiol-disulfide homeostasis, methylation, phosphorylation and proteolytic cleavage were evaluated in the serum of the evaluated subjects in the present study. Our results showed some characteristics for early ccRCC: high production of cytokines, substrate hypersialylation, induced nitrosative and carbonylic stress, arginine hypermethylation, thiol/disulfide homeostasis (TDH) alteration, the regulatory role of soluble receptors (sRAGE—soluble receptor for advanced glycation end products, sIL-6R—soluble receptor for Interleukin 6) in RAGE and IL-6 signaling, the modulatory effect of TK1—thymidine kinase 1 and TuM2-PK—tumoral pyruvate-kinase 2 in controlling the level of phosphometabolites in neoplastic cells. These data could be the initial point for development of a panel of biomarkers such as total sialic acid, orosomucoids, nitrotyrosine, carbonylic metabolites, Asymmetric Dimethylarginines (ADMA), Symmetric Dimethylarginines (SDMA), and thiol-disulfide equilibrium for early diagnosis of ccRCC. Moreover, they could be considered a specific disease posttranslational modification signature which underlines the transition from early to advanced stages in this neoplasia, and of a therapeutic target in kidney oncogenesis. Full article
(This article belongs to the Special Issue Metabolic Reprogramming: Implications in Cancer, Immune Surveillance and Regenerative Medicine)
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Review

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21 pages, 1321 KiB  
Review
YAP and TAZ Mediators at the Crossroad between Metabolic and Cellular Reprogramming
by Giorgia Di Benedetto, Silvia Parisi, Tommaso Russo and Fabiana Passaro
Metabolites 2021, 11(3), 154; https://doi.org/10.3390/metabo11030154 - 8 Mar 2021
Cited by 17 | Viewed by 3692
Abstract
Cell reprogramming can either refer to a direct conversion of a specialized cell into another or to a reversal of a somatic cell into an induced pluripotent stem cell (iPSC). It implies a peculiar modification of the epigenetic asset and gene regulatory networks [...] Read more.
Cell reprogramming can either refer to a direct conversion of a specialized cell into another or to a reversal of a somatic cell into an induced pluripotent stem cell (iPSC). It implies a peculiar modification of the epigenetic asset and gene regulatory networks needed for a new cell, to better fit the new phenotype of the incoming cell type. Cellular reprogramming also implies a metabolic rearrangement, similar to that observed upon tumorigenesis, with a transition from oxidative phosphorylation to aerobic glycolysis. The induction of a reprogramming process requires a nexus of signaling pathways, mixing a range of local and systemic information, and accumulating evidence points to the crucial role exerted by the Hippo pathway components Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding Motif (TAZ). In this review, we will first provide a synopsis of the Hippo pathway and its function during reprogramming and tissue regeneration, then we introduce the latest knowledge on the interplay between YAP/TAZ and metabolism and, finally, we discuss the possible role of YAP/TAZ in the orchestration of the metabolic switch upon cellular reprogramming. Full article
(This article belongs to the Special Issue Metabolic Reprogramming: Implications in Cancer, Immune Surveillance and Regenerative Medicine)
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