Autocrine activation of EGF receptor promotes oscillation of glutamate‐induced calcium increase in astrocytes cultured in rat cerebral cortex

Morita, Mitsuhiro; Kozuka, Nagisa; Itofusa, Rurika; Yukawa, Masashi; Kudo, Yoshihisa

doi:10.1111/j.1471-4159.2005.03430.x

Cited by 30 publications

(21 citation statements)

References 34 publications

(46 reference statements)

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“…Here, we show that extracellular HSP90␣ transiently increases cytosolic [Ca 2ϩ ] in glioblastoma U87 cells and converts calcium response induced by EGF from a transient to an oscillatory pattern. Similar calcium oscillations induced by EGF have been previously reported in astrocytes in response to glutamate (42), pro-inflammatory cytokines (41), or thimerosal, which directly activates the inositol 1,4,5- triphosphate receptor and induces calcium release from internal stores (43). These stimuli also induce release of ATP by astrocytes.…”

Section: Discussionmentioning

confidence: 48%

“…Intracellular Ca 2ϩ modulates the proliferative effects of EGF (16,39,40), and complex Ca 2ϩ oscillations are associated with human astrocytoma cell migration (25,41,42 , and activity of store-operated calcium channels. Here, we show that extracellular HSP90␣ transiently increases cytosolic [Ca 2ϩ ] in glioblastoma U87 cells and converts calcium response induced by EGF from a transient to an oscillatory pattern.…”

Section: Discussionmentioning

confidence: 99%

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Transactivation of the Epidermal Growth Factor Receptor by Heat Shock Protein 90 via Toll-like Receptor 4 Contributes to the Migration of Glioblastoma Cells

Thüringer

Hammann

Benikhlef

et al. 2011

Journal of Biological Chemistry

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Extracellular heat shock protein HSP90␣ was reported to participate in tumor cell growth, invasion, and metastasis formation through poorly understood signaling pathways. Herein, we show that extracellular HSP90␣ favors cell migration of glioblastoma U87 cells. More specifically, externally applied HSP90␣ rapidly induced endocytosis of EGFR. This response was accompanied by a transient increase in cytosolic Ca 2؉ appearing after 1-3 min of treatment. In the presence of EGF, U87 cells showed HSP90␣-induced Ca 2؉ oscillations, which were reduced by the ATP/ADPase, apyrase, and inhibited by the purinergic P 2 inhibitor, suramin, suggesting that ATP release is requested. Disruption of lipid rafts with methyl ␤-cyclodextrin impaired the Ca 2؉ rise induced by extracellular HSP90␣ combined with EGF. Specific inhibition of TLR4 expression by blocking antibodies suppressed extracellular HSP90␣-induced Ca 2؉ signaling and the associated cell migration. HSPs are known to bind lipopolysaccharides (LPSs). Preincubating cells with Polymyxin B, a potent LPS inhibitor, partially abrogated the effects of HSP90␣ without affecting Ca 2؉ oscillations observed with EGF. Extracellular HSP90␣ induced EGFR phosphorylation at Tyr-1068, and this event was prevented by both the protein kinase C␦ inhibitor, rottlerin, and the c-Src inhibitor, PP2. Altogether, our results suggest that extracellular HSP90␣ transactivates EGFR/ErbB1 through TLR4 and a PKC␦/c-Src pathway, which induces ATP release and cytosolic Ca 2؉ increase and finally favors cell migration. This mechanism could account for the deleterious effects of HSPs on high grade glioma when released into the tumor cell microenvironment.Glioma ranges from slowly growing low grade tumors to rapidly growing high grade tumors, including anaplastic astrocytoma and glioblastoma (1, 2). High grade gliomas include anaplastic tumor cells, necrotic foci, and rich vascularity, due largely to the aberrant expression of angiogenic factors by tumor cells (3). Tumor cells are highly proliferative and invasive within the brain. Despite the development of various treatments, the life expectancy of patients remains poor (4).One of the molecules that could contribute to invasion is the stress or heat shock protein 90 (HSP90). In several tumor types, cell surface expression of HSP90 correlates with metastatic potential (5), and its inhibition with antibodies (6, 7) or with cell-impermeable inhibitors (8) reduces cell migration in vitro. Of the two HSP90 isoforms, only HSP90␣ has been described extracellularly, which argues against cell lysis as the source of extracellular HSP90 (8). The metalloprotease MMP-2 can be associated with extracellular HSP90␣ (8), which is favored by acetylation of the stress protein (9). Surface HSP90␣ also participates in extracellular matrix proteininduced c-Src/integrin association and reorganization of the actin cytoskeleton (10). The cell-impermeable inhibitor of HSP90, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (DMAG)-N-oxide, displays anti-invasive and anti-meta...

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Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Transactivation of the Epidermal Growth Factor Receptor by Heat Shock Protein 90 via Toll-like Receptor 4 Contributes to the Migration of Glioblastoma Cells

Thüringer

Hammann

Benikhlef

et al. 2011

Journal of Biological Chemistry

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“…Thus far, we have observed the similar activation of NF-B in glial cells in response to treatment with either EGF or glutamate. Interestingly, similarly to mGluR5, EGFR signaling promotes calcium oscillation and its expression is increased in astrocytes in response to injury (14,22). Moreover, previous studies have shown that (23), suggesting that there is cross talk between these two signaling pathways.…”

Section: Vol 28 2008 Glutamate-induced Regulation Of Nf-b Requires mentioning

confidence: 91%

“…In one study, it was shown that mGluR5 stimulation leads to the activation of extracellular signal-regulated kinase 1/2 and the epidermal growth factor receptor (EGFR) in astrocytes (23). Similarly to mGluR5, EGFR signaling promotes Ca 2ϩ oscillation in astrocytes (22), and the EGFR is upregulated in astrocytes in response to injury (14). Interestingly, it was recently demonstrated that in the hippocampus, mGluR5 activates NF-B, an evolutionarily conserved transcription factor that has critical roles in regulating cell survival, proliferation, and immune/inflammatory responses (8).…”

mentioning

confidence: 99%

Essential Role for Epidermal Growth Factor Receptor in Glutamate Receptor Signaling to NF-κB

Sitcheran

Comb

Cogswell

et al. 2008

Molecular and Cellular Biology

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Glutamate is a critical neurotransmitter of the central nervous system (CNS) and also an important regulator of cell survival and proliferation. The binding of glutamate to metabotropic glutamate receptors induces signal transduction cascades that lead to gene-specific transcription. The transcription factor NF-B, which regulates cell proliferation and survival, is activated by glutamate; however, the glutamate receptorinduced signaling pathways that lead to this activation are not clearly defined. Here we investigate the glutamate-induced activation of NF-B in glial cells of the CNS, including primary astrocytes. We show that glutamate induces phosphorylation, nuclear accumulation, DNA binding, and transcriptional activation function of glial p65. The glutamate-induced activation of NF-B requires calcium-dependent IB kinase ␣ (IKK␣) and IKK␤ activation and induces p65-IB␣ dissociation in the absence of IB␣ phosphorylation or degradation. Moreover, glutamate-induced IKK preferentially targets the phosphorylation of p65 but not IB␣. Finally, we show that the ability of glutamate to activate NF-B requires cross-coupled signaling with the epidermal growth factor receptor. Our results provide insight into a glutamate-induced regulatory pathway distinct from that described for cytokine-induced NF-B activation and have important implications with regard to both normal glial cell physiology and pathogenesis.

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“…10,11 In addition, EGFR signaling is coupled to Ca 2+ waves, and it has been suggested that this signaling employs XPA to maintain the integrity of neuronal DNA during glutamatergic neurotransmission. [12][13][14][15] Indeed, human and animal loss-of-function mutations in the xpa gene result in neurodegeneration. 8 Nonetheless, only recently it was shown that neurons could co-express EGFR+XPA.…”

Section: Introductionmentioning

confidence: 99%

Noise Stress Induces an Epidermal Growth Factor Receptor/Xeroderma Pigmentosum–A Response in the Auditory Nerve

Guthrie

2017

J Histochem Cytochem.

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SummaryIn response to toxic stressors, cancer cells defend themselves by mobilizing one or more epidermal growth factor receptor (EGFR) cascades that employ xeroderma pigmentosum-A (XPA) to repair damaged genes. Recent experiments discovered that neurons within the auditory nerve exhibit basal levels of EGFR+XPA co-expression. This finding implied that auditory neurons in particular or neurons in general have the capacity to mobilize an EGFR+XPA defense. Therefore, the current study tested the hypothesis that noise stress would alter the expression pattern of EGFR/XPA within the auditory nerve. Design-based stereology was used to quantify the proportion of neurons that expressed EGFR, XPA, and EGFR+XPA with and without noise stress. The results revealed an intricate neuronal response that is suggestive of alterations to both co-expression and individual expression of EGFR and XPA. In both the apical and middle cochlear coils, the noise stress depleted EGFR+XPA expression. Furthermore, there was a reduction in the proportion of neurons that expressed XPA-alone in the middle coils. However, the noise stress caused a significant increase in the proportion of neurons that expressed EGFR-alone in the middle coils. The basal cochlear coils failed to mobilize a significant response to the noise stress. These results suggest that EGFR and XPA might be part of the molecular defense repertoire of the auditory nerve. (J Histochem Cytochem 65:173-184, 2017)

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Autocrine activation of EGF receptor promotes oscillation of glutamate‐induced calcium increase in astrocytes cultured in rat cerebral cortex

Cited by 30 publications

References 34 publications

Transactivation of the Epidermal Growth Factor Receptor by Heat Shock Protein 90 via Toll-like Receptor 4 Contributes to the Migration of Glioblastoma Cells

Transactivation of the Epidermal Growth Factor Receptor by Heat Shock Protein 90 via Toll-like Receptor 4 Contributes to the Migration of Glioblastoma Cells

Essential Role for Epidermal Growth Factor Receptor in Glutamate Receptor Signaling to NF-κB

Noise Stress Induces an Epidermal Growth Factor Receptor/Xeroderma Pigmentosum–A Response in the Auditory Nerve

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