Role of Sodium/Calcium Exchangers in Tumors

The sodium/calcium exchanger (NCX) is a unique calcium transport system, generally transporting calcium ions out of the cell in exchange for sodium ions. Nevertheless, under special conditions this transporter can also work in a reverse mode, in which direction of the ion transport is inverted—calcium ions are transported inside the cell and sodium ions are transported out of the cell. To date, three isoforms of the NCX have been identified and characterized in humans. Majority of information about the NCX function comes from isoform 1 (NCX1). Although knowledge about NCX function has evolved rapidly in recent years, little is known about these transport systems in cancer cells. This review aims to summarize current knowledge about NCX functions in individual types of cancer cells.

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Regulation of calcium transport in cardiac cells

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y84-002 ◽

1984 ◽

Vol 62 (1) ◽

pp. 9-22 ◽

Cited By ~ 22

Author(s):

Adil E. Shamoo ◽

Indu S. Ambudkar

Keyword(s):

Sarcoplasmic Reticulum ◽

Calcium Channel ◽

Calcium Homeostasis ◽

Calcium Transport ◽

Cardiac Cells ◽

Transport Systems ◽

Sodium Calcium Exchanger ◽

Inotropic Effects ◽

Cellular Calcium ◽

Sodium Calcium

Calcium transporting systems and the regulatory events accompanying them are pivotal in the function of the cardiac cell. The concerted involvement of the various membranes achieve cellular calcium homeostasis that can also respond to the physiological exigencies of the cell. Three membrane systems are primarily involved; the sarcolemma, sarcoplasmic reticulum, and the mitochondria. The various Ca2+ transport systems that have been described in these membranes are as follows: the calcium channel, Ca2+-ATPase, Ca2+–Mg2+ ATPase, and sodium–calcium exchanger in the sarcolemma; the Ca2+–Mg2+ ATPase and a possible calcium channel in the sarcoplasmic reticulum; and the sodium–calcium exchanger and electrophoretic calcium uniporter in the mitochondrial inner membrane. These systems mediate calcium fluxes to maintain physiological cytosolic calcium concentrations. β-Adrenergic hormones regulate calcium transport systems in sarcolemma and sarcoplasmic reticulum, while α-adrenergic hormones modulate those in the mitochondria and probably in the sarcolemma. The response to these hormones is initiated at the sarcolemma, which contains the specific receptors. Intracellularly the effects are propagated by secondary messengers, e.g., cAMP, calcium, and lipid changes. Specific proteins are also involved in these events. Phospholamban, a 22 000 dalton protein, is involved in mediating the cAMP-dependent inotropic effects, by activating the Ca2+–Mg2+ ATPase of the sarcoplasmic reticulum. Alterations in any one of the systems involved in the regulation of calcium transport or in the calcium transport systems per se, would then result in drastic alterations in the cellular calcium homeostasis. Such effects could be of significance in cellular dysfunction during cardiac disease.

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The role of hypoxia in endometrial cancer

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210224130022 ◽

2021 ◽

Vol 22 ◽

Author(s):

Yarely M. Salinas-Vera ◽

Dolores Gallardo-Rincón ◽

Erika Ruíz-García ◽

Macrina B. Silva-Cázares ◽

Carmen Sol de la Peña-Cruz ◽

...

Keyword(s):

Endometrial Cancer ◽

Cell Survival ◽

Cancer Cells ◽

Cancer Cell ◽

Targeted Therapies ◽

Current Knowledge ◽

Vasculogenic Mimicry ◽

Cellular Processes ◽

Corpus Uteri

: Endometrial cancer represents the most frequent neoplasia from the corpus uteri, and comprises the 14th leading cause of death in women worldwide. Risk factors that contribute to the disease include early menarche, late menopause, nulliparity, and menopausal hormone use, as well as hypertension and obesity comorbidities. The clinical effectiveness of chemotherapy is variable, suggesting that novel molecular targeted therapies against specific cellular processes associated with the maintenance of cancer cell survival and therapy resistance urged to ameliorate the rates of success in endometrial cancer treatment. In the course of tumor growth, cancer cells must adapt to decreased oxygen availability in the microenvironment by upregulation of hypoxia-inducible factors, which orchestrate the activation of a transcriptional program leading to cell survival. During this adaptative process, the hypoxic cancer cells may acquire invasive and metastatic properties as well as increased cell proliferation and resistance to chemotherapy, enhanced angiogenesis, vasculogenic mimicry, and maintenance of cancer cell stemness, which contribute to more aggressive cancer phenotypes. Several studies have shown that hypoxia-inducible factor 1 alpha (HIF-1α) protein is aberrantly overexpressed in many solid tumors from breast, prostate, ovarian, bladder, colon, brain, and pancreas. Thus, it has been considered an important therapeutic target. Here, we reviewed the current knowledge of the relevant roles of cellular hypoxia mechanisms and HIF-1α functions in diverse processes associated with endometrial cancer progression. In addition, we also summarize the role of microRNAs in the posttranscriptional regulation of protein-encoding genes involved in the hypoxia response in endometrial cancer. Finally, we pointed out the need for urgent targeted therapies to impair the cellular processes activated by hypoxia in the tumor microenvironment.

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Regulation of ST6GAL1 sialyltransferase expression in cancer cells

Glycobiology ◽

10.1093/glycob/cwaa110 ◽

2020 ◽

Author(s):

Kaitlyn A Dorsett ◽

Michael P Marciel ◽

Jihye Hwang ◽

Katherine E Ankenbauer ◽

Nikita Bhalerao ◽

...

Keyword(s):

Cancer Cells ◽

Translational Regulation ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Sialic Acids ◽

Invasion Resistance ◽

Cell Behaviors ◽

Molecular Events ◽

Wide Range

Abstract The ST6GAL1 sialyltransferase, which adds α2–6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress, and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics. However, despite the burgeoning interest in the role of ST6GAL1 in the phenotypic features of tumor cells, insufficient attention has been paid to the molecular mechanisms responsible for ST6GAL1 upregulation during neoplastic transformation. Evidence suggests that these mechanisms are multifactorial, encompassing genetic, epigenetic, transcriptional, and post-translational regulation. The purpose of this review is to summarize current knowledge regarding the molecular events that drive enriched ST6GAL1 expression in cancer cells.

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Genetic Evidence For Essential Role Of Sodium-Calcium Exchanger In Development Of Pulmonary Hypertension

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a4750 ◽

2012 ◽

Author(s):

Yun-Min Zheng ◽

Lin Mei ◽

Ling Dong ◽

Yong-Xiao Wang

Keyword(s):

Pulmonary Hypertension ◽

Essential Role ◽

Genetic Evidence ◽

Sodium Calcium Exchanger ◽

Sodium Calcium

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Role of p38/Akt Signaling Pathway in the Regulation of Sodium/Calcium Exchanger Expression in Adult Cardiomyocytes

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2010.06.077 ◽

2010 ◽

Vol 16 (8) ◽

pp. S22

Author(s):

Olga Chernysh ◽

Santhosh K. Mani ◽

Donald R. Menick

Keyword(s):

Signaling Pathway ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Sodium Calcium Exchanger ◽

Sodium Calcium ◽

Adult Cardiomyocytes

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On the Role of sIL-2R Measurements in Rheumatoid Arthritis and Cancers

Mediators of Inflammation ◽

10.1155/mi.2005.121 ◽

2005 ◽

Vol 2005 (3) ◽

pp. 121-130 ◽

Cited By ~ 62

Author(s):

Anna Maria Witkowska

Keyword(s):

Rheumatoid Arthritis ◽

Cancer Cells ◽

T Lymphocyte ◽

Biological Function ◽

Current Knowledge ◽

Lymphocyte Activation ◽

Soluble Receptor ◽

Disease Progress ◽

Lines Of Evidence

A soluble IL-2 receptor (sIL-2R) is a circulating form of a membrane receptor localized on lymphoid and some cancer cells. The biological function of sIL-2R has not been completely understood. Substantially, it seems to reflect T-lymphocyte activation in diseases of different pathology. Moreover, the soluble receptor has been considered, at least in part, responsible for unsuccessful immunotherapy with IL-2 in cancers. Several lines of evidence indicate sIL-2R measurements to be useful in determining disease progress and prognosis. This review summarizes current knowledge on the sIL-2R behavior in RA and solid cancers of varied etiology.

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Effect of intracellularly applied sodium ions on the dark voltage of isolated retinal rods

Visual Neuroscience ◽

10.1017/s0952523800004533 ◽

1990 ◽

Vol 4 (4) ◽

pp. 331-336 ◽

Cited By ~ 4

Author(s):

Karl-Friedrich Schmidt ◽

Gottfried N. Nöll ◽

Christian Baumann

Keyword(s):

Calcium Ions ◽

Time Course ◽

Sodium Ions ◽

Sodium Calcium ◽

Retinal Rods ◽

High Calcium ◽

Simple Medium ◽

Cytoplasmic Content ◽

Calcium Exchange ◽

Sodium Effect

AbstractIsolated retinal rods of the frog consisting of the outer segment and the ellipsoid were patch-clamped and recorded in the whole-cell mode. The recording pipettes were filled with solutions of different composition in order to alter the cytoplasmic content of sodium, phosphate, and calcium ions, and guanine nucleotides. When a simple medium with potassium as the principal cation was used, the dark voltage slowly approached more negative values. This tendency of spontaneous hyperpolarization was reduced significantly when cGMP or GTP were present in the pipette medium. Sodium ions, on the other hand, clearly increased the speed of hyperpolarization. In the presence of sodium (20 mM), the stabilizing effect of GTP did not occur and that of cGMP was clearly diminished. Phosphate (20 mM) neutralized the sodium effect. High calcium levels (100 μM) did not measurably influence the time course of hyperpolarization. We conclude that the normal cytoplasmic sodium level in rods does not exceed 10 mM and that higher internal sodium concentrations interfere with the sodium–calcium exchange mechanism.

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