Ca2+ Influx through Reverse Mode Na+/Ca2+ Exchange Is Critical for Vascular Endothelial Growth Factor-mediated Extracellular Signal-regulated Kinase (ERK) 1/2 Activation and Angiogenic Functions of Human Endothelial Cells

Andrikopoulos, Petros; Baba, Akemichi; Matsuda, Takehisa; Djamgoz, Mustafa B.A.; Yaqoob, Muhammad; Eccles, Suzanne A.

doi:10.1074/jbc.m111.251777

Cited by 68 publications

(104 citation statements)

References 61 publications

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“…In addition to directly promoting EC proliferation, migration and permeability, Ca 2þ influx through TRPs might stimulate ECs to produce and release the angiogenic growth factors VEGF, FGF and PDGF, which in turn might stimulate angiogenesis in an autocrine or paracrine manner (figure 4). It was also shown that Ca 2þ influx through the reverse mode of the NCX1 Na þ /Ca 2þ exchanger is required for VEGF-induced ERK1/2 phosphorylation and downstream EC functions in angiogenesis [100].…”

Section: Ca 2þ Remodelling In Tumour Vascularizationmentioning

confidence: 99%

Remodelling of Ca²⁺transport in cancer: how it contributes to cancer hallmarks?

Prevarskaya

Ouadid-Ahidouch²,

Skryma

et al. 2014

Phil. Trans. R. Soc. B

222

195

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Cancer involves defects in the mechanisms underlying cell proliferation, death and migration. Calcium ions are central to these phenomena, serving as major signalling agents with spatial localization, magnitude and temporal characteristics of calcium signals ultimately determining cell's fate. Cellular Ca 2+ signalling is determined by the concerted action of a molecular Ca 2+ -handling toolkit which includes: active energy-dependent Ca 2+ transporters, Ca 2+ -permeable ion channels, Ca 2+ -binding and storage proteins, Ca 2+ -dependent effectors. In cancer, because of mutations, aberrant expression, regulation and/or subcellular targeting of Ca 2+ -handling/transport protein(s) normal relationships among extracellular, cytosolic, endoplasmic reticulum and mitochondrial Ca 2+ concentrations or spatio-temporal patterns of Ca 2+ signalling become distorted. This causes deregulation of Ca 2+ -dependent effectors that control signalling pathways determining cell's behaviour in a way to promote pathophysiological cancer hallmarks such as enhanced proliferation, survival and invasion. Despite the progress in our understanding of Ca 2+ homeostasis remodelling in cancer cells as well as in identification of the key Ca 2+ -transport molecules promoting certain malignant phenotypes, there is still a lot of work to be done to transform fundamental findings and concepts into new Ca 2+ transport-targeting tools for cancer diagnosis and treatment.

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Section: Ca 2þ Remodelling In Tumour Vascularizationmentioning

confidence: 99%

Remodelling of Ca²⁺transport in cancer: how it contributes to cancer hallmarks?

Prevarskaya

Ouadid-Ahidouch²,

Skryma

et al. 2014

Phil. Trans. R. Soc. B

222

195

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“…More specifically, the close proximity between NCX and the TRPC channels, which may either physically interact [371] or be clustered in limited membrane nanodomains [372] , causes NCX to switch into the reverse-mode upon Na + accumulation beneath the plasma membrane [371,372] . Intriguingly, NCX-mediated Ca 2+ entry in ECs may be stimulated by Ach [373] , histamine [43] , and VEGF [374] , but not by ATP [375] . In particular, NCX-driven Ca 2+ influx underpins PKCα translocation to the plasma membrane, where it stimulates ERK1/2 to trigger a number of steps (proliferation, migration, and tubulogenesis) involved in VEGF-dependent angiogenesis [374] .…”

Section: +mentioning

confidence: 99%

Update on vascular endothelial Ca²⁺signalling: A tale of ion channels, pumps and transporters

Moccia

Berra‐Romani²,

Tanzi³

2012

WJBC

110

192

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A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiescence is, therefore, regarded among the early events leading to the onset and progression of potentially lethal diseases, such as hypertension, myocardial infarction, brain stroke, and tumor. Intracellular Ca 2+ signals have long been know to play a central role in the complex network of signaling pathways regulating the endothelial functions. Notably, recent work has outlined how any change in the pattern of expression of endothelial channels, transporters and pumps involved in the modulation of intracellular Ca 2+ levels may dramatically affect whole body homeostasis. Vascular ECs may react to both mechanical and chemical stimuli by generating a variety of intracellular Ca 2+ signals, ranging from brief, localized Ca 2+ pulses to prolonged Ca 2+ oscillations engulfing the whole cytoplasm. The well-defined spatiotemporal profile of the subcellular Ca 2+ signals elicited in ECs by specific extracellular inputs depends on the interaction between Ca 2+ releasing channels, which are located both on the plasma membrane and in a number of intracellular organelles, and Ca 2+ removing systems. The present article aims to summarize both the past and recent literature in the field to provide a clear-cut picture of our current knowledge on the molecular nature and the role played by the components of the Ca 2+ machinery in vascular ECs under both physiological and pathological conditions.

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“…As already described above ( paragraph on VCSCs), an intriguing example has been described in HUVEC, in which a coupling between NCX and VGSCs occurs [39].…”

Section: (A) Sodium -Proton Exchangermentioning

confidence: 99%

“…VGSC activity potentiates VEGF-induced ERK1/2 activation by attenuating membrane depolarization, altering [Ca 2þ ]i kinetics and PKC activity and thus increasing cellular proliferation, chemotaxis and tubulogenesis [36] (table 1 and figure 2). Moreover, Ca 2þ inflow through reverse mode sodium-calcium exchanger (NCX) is required for PKC activation and targeting to the plasma membrane, as well as for VEGF-induced ERK1/2 phosphorylation and downstream EC functions in angiogenesis [39] (see also §7). The data unveil an intriguing mechanism for the control of Vm in non-excitable cells by VGSCs in response to physiological stimuli in vitro.…”

Section: Voltage-gated Channelsmentioning

confidence: 99%

“…HMEC, human microvascular EC; HPAEC, human pulmonary artery EC; HUVEC, human umbilical vein EC; EA.hy926, EC line derived from HUVEC fused with human lung adenocarcinoma cell line A549; PAEC, porcine aortic endothelial cells; BTEC, tumour-derived EC from breast carcinoma; H5VEC, heart endothelioma (H5V) EC; MAEC, mouse aortic EC; EPC, endothelial progenitor cells; RCC-EPC, EPC isolated from renal carcinoma patients; Numbers in parenthesis indicate the respective reference number. EPC [30] HMEC [31] BTEC [32] RCC-EPC [29] HUVEC [33 -35] HUVEC [36] HUVEC [37] HUVEC [38] HUVEC [36,39] MAEC from KO mice [40] HMEC [41,42] EPC [43] survival and proliferation RCC-EPC [29] EPC [30] HMEC [31] HUVEC [44] PAEC [45] H5V EC [46] HUVEC [40] HUVEC, HMEC [41,55] EPC [43] permeability HMEC,HUVEC [56 -58] HPAEC [59] Frog mesenteric microvessels [60] H5V EC [46] HUVEC [61] in vivo angiogenesis zebrafish [62] CAM [44] collateral growth [45] HERG-1-Retinoblastoma [63] EAG1-Xenograft in SCID mice and human osteosarcoma [27,28] CAM [54] xenograft in nude mice [38] Rabbit cornea [64] human mammary carcinoma, glioblastoma [65,66] AQP1 KO mice and C57BL/ 6 mice …”

Section: Transient Receptor Potential Proteins and Stim1-orai1 Complexmentioning

confidence: 99%

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Functional properties of ion channels and transporters in tumour vascularization

Fiorio

Munaron

2014

Phil. Trans. R. Soc. B

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Vascularization is crucial for solid tumour growth and invasion, providing metabolic support and sustaining metastatic dissemination. It is now accepted that ion channels and transporters play a significant role in driving the cancer growth at all stages. They may represent novel therapeutic, diagnostic and prognostic targets for anti-cancer therapies. On the other hand, although the expression and role of ion channels and transporters in the vascular endothelium is well recognized and subject of recent reviews, only recently has their involvement in tumour vascularization been recognized. Here, we review the current literature on ion channels and transporters directly involved in the angiogenic process. Particular interest will be focused on tumour angiogenesis in vivo as well as in the different steps that drive this process in vitro , such as endothelial cell proliferation, migration, adhesion and tubulogenesis. Moreover, we compare the ‘transportome’ system of tumour vascular network with the physiological one.

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Ca2+ Influx through Reverse Mode Na+/Ca2+ Exchange Is Critical for Vascular Endothelial Growth Factor-mediated Extracellular Signal-regulated Kinase (ERK) 1/2 Activation and Angiogenic Functions of Human Endothelial Cells

Cited by 68 publications

References 61 publications

Remodelling of Ca²⁺transport in cancer: how it contributes to cancer hallmarks?

Remodelling of Ca²⁺transport in cancer: how it contributes to cancer hallmarks?

Update on vascular endothelial Ca²⁺signalling: A tale of ion channels, pumps and transporters

Functional properties of ion channels and transporters in tumour vascularization

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Ca2+ Influx through Reverse Mode Na+/Ca2+ Exchange Is Critical for Vascular Endothelial Growth Factor-mediated Extracellular Signal-regulated Kinase (ERK) 1/2 Activation and Angiogenic Functions of Human Endothelial Cells

Cited by 68 publications

References 61 publications

Remodelling of Ca2+transport in cancer: how it contributes to cancer hallmarks?

Remodelling of Ca2+transport in cancer: how it contributes to cancer hallmarks?

Update on vascular endothelial Ca2+signalling: A tale of ion channels, pumps and transporters

Functional properties of ion channels and transporters in tumour vascularization

Contact Info

Product

Resources

About

Remodelling of Ca²⁺transport in cancer: how it contributes to cancer hallmarks?

Remodelling of Ca²⁺transport in cancer: how it contributes to cancer hallmarks?

Update on vascular endothelial Ca²⁺signalling: A tale of ion channels, pumps and transporters