Heregulinβ activates store-operated Ca2+ channels through c-erbB2 receptor level-dependent pathway in human breast cancer cells

Liao, Jingwen; Li, Linlin; Wang, Qun; Yue, Jiachang

doi:10.1016/j.abb.2006.12.003

Cited by 6 publications

(3 citation statements)

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“…Other agonists that can trigger an elevation in [Ca 2+ ] i involved in motility control are the neurotransmitter GABA, that exerts an excitatory action in immature cells due to the high intracellular Cl - concentration, the neuropeptide somatostatin that influences Ca 2+ fluctuations in a stage-dependent manner, and neurotrophins, like Brain Derived Neurotrophic Factor [13,43-45]. The ErbB4 receptor, like other members of the ErbB family [46,47], upon ligand activation could elicit calcium release from intracellular stores and calcium influx. However, there are no data available for this mechanism in neuronal cells, apart form a report [48] indicating that NRG1 can modulate glutamate-induced [Ca 2+ ] i increase.…”

Section: Discussionmentioning

confidence: 99%

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

et al. 2011

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BackgroundA number of studies have separately shown that the neuregulin1 (NRG1)/ErbB4 system and NMDA-type glutamate receptors (NMDARs) are involved in several aspects of neuronal migration. In addition, intracellular calcium fluctuations play central roles in neuronal motility. Stable expression of the tyrosine kinase receptor ErbB4 promotes migratory activity in the neural progenitor cell line ST14A upon NRG1 stimulation. In this work we analyzed the potential interactions between the NRG1/ErbB4 system and NMDARs in the ST14A migratory process as well as its calcium dependence.ResultsRT-PCR studies have shown that both native ST14A cells (non-expressing ErbB4), as well as ErbB4-transfected cells express low levels of a restricted number of NMDAR subunits: NR1, NR2C, NR2D and NR3B. The resulting NMDAR would form Ca2+ channels characterized by low Mg2+-sensitivity and low Ca2+-permeability, generating small, long-lasting currents. Ca2+-imaging experiments showed slow [Ca2+]i increases in 45% of the cells following 8 μM NMDA stimulation. Basal migration of ErbB4-transfected ST14A cells was unaffected by 18 hrs NMDA incubation. However, over the same incubation time, NMDA was able to significantly enhance NRG1-induced migration. Pre-incubation with the intracellular calcium chelator BAPTA-AM reduced both NRG1- and NRG1/NMDA-stimulated migration, suggesting the involvement of Ca2+ in these processes. NRG1 stimulation of ErbB4-transfected ST14A cells induced a sustained, long-lasting increase in [Ca2+]i, in 99% of the cells. These intracellular Ca2+ signals could be ascribed to both release from intracellular stores and influx from the extracellular medium trough a mechanism of store-operated calcium entry (SOCE). Short-time co-incubation of NMDA and NRG1 did not substantially modify the NRG1-induced intracellular calcium signals.ConclusionsIn summary, NRG1 stimulation of the ErbB4 receptor exerts a sustained [Ca2+]i increase in ST14A neural progenitors; NRG1-induced migration is Ca2+-dependent and can be positively modulated by activation of the NMDA receptor.

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Section: Discussionmentioning

confidence: 99%

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

et al. 2011

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“…Store-operated Ca 2+ channels have been shown to play an important role in Ca 2+ influx in different human breast cancer cells. , Therefore, the role of store-operated Ca 2+ channels was explored in 1 -induced [Ca 2+ ] i levels. These three compounds have often been applied as blockers of store-operated Ca 2+ entry in different breast cancer cell types including ZR-75-1 cells which our study used. − Our study shows that 2-APB inhibited 1 -induced [Ca 2+ ] i increases by approximately 50% in Ca 2+ -containing medium, which was similar to the magnitude of 1 -induced Ca 2+ influx.…”

Section: Resultsmentioning

confidence: 99%

“…33 Therefore, it appears that 1 has different Ca 2+ Store-operated Ca 2+ channels have been shown to play an important role in Ca 2+ influx in different human breast cancer cells. 34,35 Therefore, the role of store-operated Ca 2+ channels was explored in 1-induced [Ca 2+ ] i levels. These three compounds have often been applied as blockers of store-operated Ca 2+ entry in different breast cancer cell types including ZR-75-1 cells which our study used.…”

Section: Journal Of Natural Productsmentioning

confidence: 99%

The Mechanism of Ca²⁺ Movement in the Involvement of Baicalein-Induced Cytotoxicity in ZR-75-1 Human Breast Cancer Cells

et al. 2015

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Baicalein (5,6,7-trihydroxyflavone) (1) has been found to be active against a wide variety of cancer cells. However, the molecular mechanism underlying the effects of 1 on the induction of Ca(2+) movement and cytotoxicity in human breast cancer cells is unknown. This study examined the relationship between 1-induced Ca(2+) signaling and cytotoxicity in ZR-75-1 human breast cancer cells. The in vitro investigations reported herein produced the following results: (i) Compound 1 increased intracellular Ca(2+) concentration ([Ca(2+)]i) in a concentration-dependent manner. The signal was decreased by approximately 50% by removal of extracellular Ca(2+). (ii) Compound 1-triggered [Ca(2+)]i increases were significantly suppressed by store-operated Ca(2+) channel blockers 2-aminoethoxydiphenyl borate (2-APB) and the PKC inhibitor GF109203X. (iii) In Ca(2+)-free medium, compound 1-induced [Ca(2+)]i increases were also inhibited by GF109203X. Furthermore, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 2,5-ditert-butylhydroquinone (BHQ) abolished 1-induced [Ca(2+)]i increases. Inhibition of phospholipase C (PLC) with U73122 abolished 1-induced [Ca(2+)]i increases. (iv) Compound 1 (20-40 μM) caused cytotoxicity, increased reactive oxygen species (ROS) production, and activated caspase-9/caspase-3. Furthermore, compound 1-induced apoptosis was significantly inhibited by prechelating cytosolic Ca(2+) with BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester) or by decreasing ROS with the antioxidant NAC (N-acetylcysteine). Together, baicalein (1) induced a [Ca(2+)]i increase by inducing PLC-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via PKC-dependent, 2-APB-sensitive store-operated Ca(2+) channels. Moreover, baicalein (1) induced Ca(2+)-associated apoptosis involved ROS production in ZR-75-1 cells.

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The HER2 Signaling Network in Breast Cancer—Like a Spider in its Web

Dittrich

Gautrey

Browell

et al. 2014

J Mammary Gland Biol Neoplasia

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The human epidermal growth factor receptor 2 (HER2) is a major player in the survival and proliferation of tumour cells and is overexpressed in up to 30 % of breast cancer cases. A considerable amount of work has been undertaken to unravel the activity and function of HER2 to try and develop effective therapies that impede its action in HER2 positive breast tumours. Research has focused on exploring the HER2 activated phosphoinositide-3-kinase (PI3K)/AKT and rat sarcoma/mitogen-activated protein kinase (RAS/MAPK) pathways for therapies. Despite the advances, cases of drug resistance and recurrence of disease still remain a challenge to overcome. An important aspect for drug resistance is the complexity of the HER2 signaling network. This includes the crosstalk between HER2 and hormone receptors; its function as a transcription factor; the regulation of HER2 by protein-tyrosine phosphatases and a complex network of positive and negative feedback-loops. This review summarises the current knowledge of many different HER2 interactions to illustrate the complexity of the HER2 network from the transcription of HER2 to the effect of its downstream targets. Exploring the novel avenues of the HER2 signaling could yield a better understanding of treatment resistance and give rise to developing new and more effective therapies.

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Heregulinβ activates store-operated Ca2+ channels through c-erbB2 receptor level-dependent pathway in human breast cancer cells

Cited by 6 publications

References 30 publications

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

The Mechanism of Ca²⁺ Movement in the Involvement of Baicalein-Induced Cytotoxicity in ZR-75-1 Human Breast Cancer Cells

The HER2 Signaling Network in Breast Cancer—Like a Spider in its Web

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Heregulinβ activates store-operated Ca2+ channels through c-erbB2 receptor level-dependent pathway in human breast cancer cells

Cited by 6 publications

References 30 publications

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

The Mechanism of Ca2+ Movement in the Involvement of Baicalein-Induced Cytotoxicity in ZR-75-1 Human Breast Cancer Cells

The HER2 Signaling Network in Breast Cancer—Like a Spider in its Web

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The Mechanism of Ca²⁺ Movement in the Involvement of Baicalein-Induced Cytotoxicity in ZR-75-1 Human Breast Cancer Cells