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Special Issue "Amino Acid Transporters and Signaling in Cancer"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 June 2021).

Special Issue Editors

Dr. Barrie P. Bode
E-Mail Website
Guest Editor
Department of Biological Sciences, Northern Illinois University, DeKalb, IL 60115, USA
Interests: amino acid transporters; cancer; glutamine metabolism
Dr. Neetika Khurana
E-Mail
Guest Editor
Department of Biological Sciences, Northern Illinois University, DeKalb, IL 60115, USA

Special Issue Information

Dear Colleagues,

Metabolic reprogramming in cancer is recognized as a common and integral component of multistep tumorigenesis. Among nutrients, amino acids are central to growth signaling and cellular stress responses; likewise, the cellular machinery involved in delivering and sustaining the amino acid ecosystem is often altered in the course of cancer metabolic reprogramming. As such, amino acid transporters, metabolic enzymes, and signaling proteins are actively investigated as potential targets for cancer therapies. This Special Issue of the International Journal of Molecular Sciences focuses on the role of amino acid transporters and linked signaling proteins involved in cell-autonomous cancer growth and tumorigenesis. Papers are sought particularly in the area of transporter targeting and its effects on metabolism, growth, and stress response signaling in cancer cells and the tumors that they spawn. This rapidly emerging area of research is poised to be an integral component of advances in cancer therapy either directly, or as an adjuvant, as we move into the 2020s.

Dr. Barrie P. Bode
Dr. Neetika Khurana
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.

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Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Amino acid transporter
  • Cancer
  • Integrated stress response
  • Glutathione
  • mTOR
  • Tumorigenesis
  • Glutamine
  • Metabolism
  • Oxidative stress
  • Cell growth

Published Papers (3 papers)

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Research

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Article
Tyrosine–Chlorambucil Conjugates Facilitate Cellular Uptake through L-Type Amino Acid Transporter 1 (LAT1) in Human Breast Cancer Cell Line MCF-7
Int. J. Mol. Sci. 2020, 21(6), 2132; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062132 - 20 Mar 2020
Cited by 1 | Viewed by 1230
Abstract
l-type amino acid transporter 1 (LAT1) is an amino acid transporter that is overexpressed in several types of cancer and, thus, it can be a potential target for chemotherapy. The objectives of this study were to (a) synthesize LAT1-targeted chlorambucil derivatives and [...] Read more.
l-type amino acid transporter 1 (LAT1) is an amino acid transporter that is overexpressed in several types of cancer and, thus, it can be a potential target for chemotherapy. The objectives of this study were to (a) synthesize LAT1-targeted chlorambucil derivatives and (b) evaluate their LAT1-mediated cellular uptake as well as antiproliferative activity in vitro in the human breast cancer MCF-7 cell line. Chlorambucil was conjugated to l-tyrosine—an endogenous LAT1 substrate—via either ester or amide linkage (compounds 1 and 2, respectively). While chlorambucil itself did not bind to LAT1, its derivatives 1 and 2 bound to LAT1 with a similar affinity as with l-tyrosine and their respective cellular uptake was significantly higher than that of chlorambucil in MCF-7. The results of our cellular uptake study are indicative of antiproliferative activity, as a higher intracellular uptake of chlorambucil derivatives resulted in greater cytotoxicity than chlorambucil by itself. LAT1 thus contributes to intracellular uptake of chlorambucil derivatives and, therefore, increases antiproliferative activity. The understanding gained from our research can be used in the development of LAT1-targeted anticancer drugs and prodrugs for site-selective and enhanced chemotherapeutic activity. Full article
(This article belongs to the Special Issue Amino Acid Transporters and Signaling in Cancer)
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Review

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Review
Amino Acid Transporters Are a Vital Focal Point in the Control of mTORC1 Signaling and Cancer
Int. J. Mol. Sci. 2021, 22(1), 23; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010023 - 22 Dec 2020
Cited by 4 | Viewed by 1160
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) integrates signals from growth factors and nutrients to control biosynthetic processes, including protein, lipid, and nucleic acid synthesis. Dysregulation in the mTORC1 network underlies a wide array of pathological states, including metabolic diseases, neurological disorders, [...] Read more.
The mechanistic target of rapamycin complex 1 (mTORC1) integrates signals from growth factors and nutrients to control biosynthetic processes, including protein, lipid, and nucleic acid synthesis. Dysregulation in the mTORC1 network underlies a wide array of pathological states, including metabolic diseases, neurological disorders, and cancer. Tumor cells are characterized by uncontrolled growth and proliferation due to a reduced dependency on exogenous growth factors. The genetic events underlying this property, such as mutations in the PI3K-Akt and Ras-Erk signaling networks, lead to constitutive activation of mTORC1 in nearly all human cancer lineages. Aberrant activation of mTORC1 has been shown to play a key role for both anabolic tumor growth and resistance to targeted therapeutics. While displaying a growth factor-independent mTORC1 activity and proliferation, tumors cells remain dependent on exogenous nutrients such as amino acids (AAs). AAs are an essential class of nutrients that are obligatory for the survival of any cell. Known as the building blocks of proteins, AAs also act as essential metabolites for numerous biosynthetic processes such as fatty acids, membrane lipids and nucleotides synthesis, as well as for maintaining redox homeostasis. In most tumor types, mTORC1 activity is particularly sensitive to intracellular AA levels. This dependency, therefore, creates a targetable vulnerability point as cancer cells become dependent on AA transporters to sustain their homeostasis. The following review will discuss the role of AA transporters for mTORC1 signaling in cancer cells and their potential as therapeutic drug targets. Full article
(This article belongs to the Special Issue Amino Acid Transporters and Signaling in Cancer)
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Review
Amino Acid Transporters as Targets for Cancer Therapy: Why, Where, When, and How
Int. J. Mol. Sci. 2020, 21(17), 6156; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176156 - 26 Aug 2020
Cited by 12 | Viewed by 1253
Abstract
Amino acids are indispensable for the growth of cancer cells. This includes essential amino acids, the carbon skeleton of which cannot be synthesized, and conditionally essential amino acids, for which the metabolic demands exceed the capacity to synthesize them. Moreover, amino acids are [...] Read more.
Amino acids are indispensable for the growth of cancer cells. This includes essential amino acids, the carbon skeleton of which cannot be synthesized, and conditionally essential amino acids, for which the metabolic demands exceed the capacity to synthesize them. Moreover, amino acids are important signaling molecules regulating metabolic pathways, protein translation, autophagy, defense against reactive oxygen species, and many other functions. Blocking uptake of amino acids into cancer cells is therefore a viable strategy to reduce growth. A number of studies have used genome-wide silencing or knock-out approaches, which cover all known amino acid transporters in a large variety of cancer cell lines. In this review, these studies are interrogated together with other databases to identify vulnerabilities with regard to amino acid transport. Several themes emerge, such as synthetic lethality, reduced redundancy, and selective vulnerability, which can be exploited to stop cancer cell growth. Full article
(This article belongs to the Special Issue Amino Acid Transporters and Signaling in Cancer)
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