Special Issue "Metabolic Reprogramming and Vulnerabilities in Cancer"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 April 2019)

Special Issue Editors

Guest Editor
Dr. Deepak Nagrath

Department of Biomedical Engineering, Department of Chemical Engineering, University of Michigan, NCRC, Bldg 28, Room 3048W, 2800 Plymouth Rd, Ann Arbor, MI 48109, USA
Website | E-Mail
Phone: +1-734-764-9889
Interests: cancer metabolism; tumor microenvironment; metabolic profiling; systems biology; metabolomics
Guest Editor
Dr. Costas Lyssiotis

Department of Molecular and Integrative Physiology; Division of Gastroenterology, Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan Room 6308, 1150 East Medical Center Drive, Ann Arbor, MI 48109, USA
Website | E-Mail
Interests: : tumor metabolism; pancreatic cancer; metabolomics; stromal metabolism; immunometabolism

Special Issue Information

The dysregulated metabolic traits of cancer are not confined to malignant cells; solid tumors systemically reprogram their metabolism to create a unique metabolic microenvironment to sustain tumorigenic properties. Alterations in extrinsic and intrinsic signals in tumors dictate how metabolic rewiring occurs. Rewired metabolism not only provides a selective advantage to malignant cells in nutrient-stressed and hypoxic environments, but also facilitates invasion, metastasis, immune suppression, drug resistance, and tumor-promoting epigenetic modifications. However, recent studies have highlighted an inherent complexity of dissecting metabolic mechanisms driving tumorigenesis. One aspect of this complexity is due to the impact of metabolic alterations on epigenetic modifications and DNA damage repair. Metabolic pathways responsible for regulating methyl and acetyl levels create a reciprocal feedback loop between metabolism and genetic reprogramming in tumors. We expect new studies elucidating how tumors rewire to provide substrates for chromatin regulation. Further, with the increasing interest in mitochondrial metabolism and its role as a signaling organelle, we expect studies focused on the effect of ROS on DNA damage, and regulation of NAD metabolism for sirtuin-mediated DNA damage repair.

The other aspect of complexity in metabolic reprogramming is due to intratumoral heterogeneity. Reactive stroma are important players in the metabolic interactions within the tumor microenvironment (TME). Cancer cells reprogram stromal cells to help meet there high bioenergetic demands via secreted metabolites, exosomes, proteins, and lipids. Rewired cancer metabolism can also create an immunosuppressive microenvironment that actively inhibits the antitumor response of T-cells and natural killer cells. Therefore, there is a growing interest in reversing the tumor-supporting properties of reactive stroma for therapeutic benefits. New studies are expected to focus on modulating stromal metabolism to improve immunotherapy response or inhibit pathways supporting cancer metabolism. The unique composition of the TME has also come under scientific scrutiny leading to the discovery of cancer cells utilizing exosomes, extracellular proteins and apoptotic bodies as fuel sources. We expect novel studies on non-canonical nutrient sources that can be selectively targeted in cancer cells. Thus, strategies targeting TME metabolism have the potential to elicit a systemic anti-tumor response in contrast to cancer-specific targets of antineoplastic drugs.

Contemporary research has demonstrated that the influence of cancer metabolism on the portfolio of cancer hallmarks is prevalent and has proven that it can be used to our advantage. Discovering and dissecting tumor-specific metabolic mechanisms will open new avenues of targeting metabolic vulnerabilities in cancers. In summary, this issue will highlight emerging aspects of metabolic reprogramming on tumor phenotype with a focus on exploiting these idiosyncratic metabolic mechanisms for therapeutic benefit.

Dr. Deepak Nagrath
Dr. Costas Lyssiotis
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 papers will be 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. Cancers 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 1800 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.

Published Papers (1 paper)

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Open AccessArticle Rac-Mediated Macropinocytosis of Extracellular Protein Promotes Glucose Independence in Non-Small Cell Lung Cancer
Received: 26 November 2018 / Revised: 23 December 2018 / Accepted: 28 December 2018 / Published: 2 January 2019
PDF Full-text (2940 KB) | HTML Full-text | XML Full-text | Supplementary Files
Cancer cells can adapt to nutrient poor conditions by rewiring their metabolism and using alternate fuel sources. Identifying these adaptive metabolic pathways may provide novel targets for cancer therapy. Here, we identify a subset of non-small cell lung cancer (NSCLC) cell lines that [...] Read more.
Cancer cells can adapt to nutrient poor conditions by rewiring their metabolism and using alternate fuel sources. Identifying these adaptive metabolic pathways may provide novel targets for cancer therapy. Here, we identify a subset of non-small cell lung cancer (NSCLC) cell lines that survive in the absence of glucose by internalizing and metabolizing extracellular protein via macropinocytosis. Macropinocytosis is increased in these glucose independent cells, and is regulated by phosphoinositide 3-kinase (PI3K) activation of Rac-Pak signaling. Furthermore, inhibition of Rac-dependent macropinocytosis blocks glucose-independent proliferation. We find that degradation of internalized protein produces amino acids, including alanine, which generates TCA cycle and glycolytic intermediates in the absence of glucose. In this process, the conversion of alanine to pyruvate by alanine transaminase 2 (ALT2) is critical for survival during glucose starvation. Collectively, Rac driven macropinocytosis of extracellular protein is an adaptive metabolic pathway used by a subset of lung cancers to survive states of glucose deprivation, and may serve as a potential drug target for cancer therapy. Full article
(This article belongs to the Special Issue Metabolic Reprogramming and Vulnerabilities in Cancer)

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