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19 pages, 3723 KB

Open AccessArticle

Space Environment Impacts Homeostasis: Exposure to Spaceflight Alters Mammary Gland Transportome Genes

by Osman V. Patel, Charlyn Partridge and Karen Plaut

Biomolecules 2023, 13(5), 872; https://doi.org/10.3390/biom13050872 - 22 May 2023

Cited by 1 | Viewed by 2999

Membrane transporters and ion channels that play an indispensable role in metabolite trafficking have evolved to operate in Earth’s gravity. Dysregulation of the transportome expression profile at normogravity not only affects homeostasis along with drug uptake and distribution but also plays a key role in the pathogenesis of diverse localized to systemic diseases including cancer. The profound physiological and biochemical perturbations experienced by astronauts during space expeditions are well-documented. However, there is a paucity of information on the effect of the space environment on the transportome profile at an organ level. Thus, the goal of this study was to analyze the effect of spaceflight on ion channels and membrane substrate transporter genes in the periparturient rat mammary gland. Comparative gene expression analysis revealed an upregulation (p < 0.01) of amino acid, Ca²⁺, K⁺, Na⁺, Zn²⁺, Cl⁻, PO₄³⁻, glucose, citrate, pyruvate, succinate, cholesterol, and water transporter genes in rats exposed to spaceflight. Genes associated with the trafficking of proton-coupled amino acids, Mg²⁺, Fe²⁺, voltage-gated K⁺-Na⁺, cation-coupled chloride, as well as Na⁺/Ca²⁺ and ATP-Mg/Pi exchangers were suppressed (p < 0.01) in these spaceflight-exposed rats. These findings suggest that an altered transportome profile contributes to the metabolic modulations observed in the rats exposed to the space environment. Full article

(This article belongs to the Collection Metabolomics and Integrated Multi-Omics in Health and Disease)

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21 pages, 2267 KB

Open AccessReview

Ca²⁺ Transportome and the Interorganelle Communication in Hepatocellular Carcinoma

by Hong-Toan Lai, Reynand Jay Canoy, Michelangelo Campanella, Yegor Vassetzky and Catherine Brenner

Cells 2022, 11(5), 815; https://doi.org/10.3390/cells11050815 - 26 Feb 2022

Cited by 8 | Viewed by 4638

Abstract

Hepatocellular carcinoma (HCC) is a type of liver cancer with a poor prognosis for survival given the complications it bears on the patient. Though damages to the liver are acknowledged prodromic factors, the precise molecular aetiology remains ill-defined. However, many genes coding for proteins involved in calcium (Ca²⁺) homeostasis emerge as either mutated or deregulated. Ca²⁺ is a versatile signalling messenger that regulates functions that prime and drive oncogenesis, favouring metabolic reprogramming and gene expression. Ca²⁺ is present in cell compartments, between which it is trafficked through a network of transporters and exchangers, known as the Ca²⁺ transportome. The latter regulates and controls Ca²⁺ dynamics and tonicity. In HCC, the deregulation of the Ca²⁺ transportome contributes to tumorigenesis, the formation of metastasizing cells, and evasion of cell death. In this review, we reflect on these aspects by summarizing the current knowledge of the Ca²⁺ transportome and overviewing its composition in the plasma membrane, endoplasmic reticulum, and the mitochondria. Full article

(This article belongs to the Section Mitochondria)

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25 pages, 2541 KB

Open AccessReview

The Role of TRP Channels in the Metastatic Cascade

by Benedikt Fels, Etmar Bulk, Zoltán Pethő and Albrecht Schwab

Pharmaceuticals 2018, 11(2), 48; https://doi.org/10.3390/ph11020048 - 17 May 2018

Cited by 68 | Viewed by 8378

Abstract

A dysregulated cellular Ca²⁺ homeostasis is involved in multiple pathologies including cancer. Changes in Ca²⁺ signaling caused by altered fluxes through ion channels and transporters (the transportome) are involved in all steps of the metastatic cascade. Cancer cells thereby “re-program” and “misuse” the cellular transportome to regulate proliferation, apoptosis, metabolism, growth factor signaling, migration and invasion. Cancer cells use their transportome to cope with diverse environmental challenges during the metastatic cascade, like hypoxic, acidic and mechanical cues. Hence, ion channels and transporters are key modulators of cancer progression. This review focuses on the role of transient receptor potential (TRP) channels in the metastatic cascade. After briefly introducing the role of the transportome in cancer, we discuss TRP channel functions in cancer cell migration. We highlight the role of TRP channels in sensing and transmitting cues from the tumor microenvironment and discuss their role in cancer cell invasion. We identify open questions concerning the role of TRP channels in circulating tumor cells and in the processes of intra- and extravasation of tumor cells. We emphasize the importance of TRP channels in different steps of cancer metastasis and propose cancer-specific TRP channel blockade as a therapeutic option in cancer treatment. Full article

(This article belongs to the Special Issue Transient Receptor Potential Ion Channels as Targets in Anti-Cancer Therapies)

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