Meta-Analysis of Public Microarray Datasets Reveals Voltage-Gated Calcium Gene Signatures in Clinical Cancer Patients

Wang, Chih‐Yang; Lai, Ming Derg; Phan, Nam Nhut; Sun, Zhonghua; Lin, Yen Chang

doi:10.1371/journal.pone.0125766

Cited by 94 publications

(110 citation statements)

References 137 publications

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“…Nevertheless, several studies report roles for L-type calcium channels in many other cell types including fibroblasts, kidney cells and endometrial and prostate cancer cells363738. In addition, analyses of available gene expression data sets by us (this study) and others25 revealed a wide expression of L-type calcium channels in many cancer cell lines and clinical samples. In particular, CACNA1D , which localizes to filopodia tips and contributes to cancer cell invasion in vitro (shown in this study), was found to be expressed in patient samples in all major breast cancer subtypes.…”

Section: Discussionmentioning

confidence: 62%

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L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling

et al. 2016

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Mounting in vitro, in vivo and clinical evidence suggest an important role for filopodia in driving cancer cell invasion. Using a high-throughput microscopic-based drug screen, we identify FDA-approved calcium channel blockers (CCBs) as potent inhibitors of filopodia formation in cancer cells. Unexpectedly, we discover that L-type calcium channels are functional and frequently expressed in cancer cells suggesting a previously unappreciated role for these channels during tumorigenesis. We further demonstrate that, at filopodia, L-type calcium channels are activated by integrin inside-out signalling, integrin activation and Src. Moreover, L-type calcium channels promote filopodia stability and maturation into talin-rich adhesions through the spatially restricted regulation of calcium entry and subsequent activation of the protease calpain-1. Altogether we uncover a novel and clinically relevant signalling pathway that regulates filopodia formation in cancer cells and propose that cycles of filopodia stabilization, followed by maturation into focal adhesions, directs cancer cell migration and invasion.

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Section: Discussionmentioning

confidence: 62%

“…4E). CACNA1D expression was also found to be upregulated in breast cancer Oncomine data sets25 and was the most commonly expressed L-type calcium channel α1 subunit in breast and pancreatic cancer cell lines (Supplementary Fig. 3B,C).…”

Section: Resultsmentioning

confidence: 91%

L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling

et al. 2016

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“…A recent meta-analysis of microarray datasets revealed VGCCs mRNA gene profile of different types of cancers 41 . L-type Ca 2+ channels are implicated in the development and progression of several tumors, such as significantly up-regulated in colon and esophageal cancers.…”

Section: Altered Ca2+ Channels/transporters In Cancermentioning

confidence: 99%

Targeting calcium signaling in cancer therapy

Cui¹,

Merritt

et al. 2017

Acta Pharmaceutica Sinica B

461

346

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The intracellular calcium ions (Ca2+) act as second messenger to regulate gene transcription, cell proliferation, migration and death. Accumulating evidences have demonstrated that intracellular Ca2+ homeostasis is altered in cancer cells and the alteration is involved in tumor initiation, angiogenesis, progression and metastasis. Targeting derailed Ca2+ signaling for cancer therapy has become an emerging research area. This review summarizes some important Ca2+ channels, transporters and Ca2+-ATPases, which have been reported to be altered in human cancer patients. It discusses the current research effort toward evaluation of the blockers, inhibitors or regulators for Ca2+ channels/transporters or Ca2+-ATPase pumps as anti-cancer drugs. This review is also aimed to stimulate interest in, and support for research into the understanding of cellular mechanisms underlying the regulation of Ca2+ signaling in different cancer cells, and to search for novel therapies to cure these malignancies by targeting Ca2+ channels or transporters.

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“…This process implies in changes in protooncogenes, genes proapoptotic genes, and DNA repair genes 22 L-type VACC has been implicated in the development and progression of several tumors, and a recent meta-analysis of microarray datasets showed VACC mRNA gene profile of different types of cancers 35 .…”

Section: Introductionmentioning

confidence: 99%

A Novel Alternative for Cancer Therapy: Pharmacological Modulation of Ca2+/cAMP Intracellular Signaling Interaction

Neto¹,

Errante²,

Bueno³

et al. 2017

Am J Pharmacol Pharmacother

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A B S T R A C TCancer is a major public health problem and the second leading cause of mortality around the world. Cancer therapy has been growing in an unprecedented fashion in the past two decades. Specific gene mutation, protein dysfunction, dysregulation of intracellular signaling pathways, and immune response had been targeted. It has been shown that the dysregulation of intracellular signaling pathways mediated by Ca 2+ and cAMP participates in the cancer initiation, tumor formation, tumor progression, metastasis, invasion and angiogenesis. Thereby, proteins involved in these pathways, such as Ca 2+ channels and cAMP-dependent protein kinase (PKA), represent potential drugs targets for cancer therapy. We recently discovered that the interaction between intracellular signaling pathways mediated by Ca 2+ and cAMP (Ca 2+ /cAMP signaling interaction) participates in the regulation of several cellular responses, including neurotransmitter/hormone secretion and neuroprotection. Due to importance of the Ca 2+ /cAMP signaling in the regulation of cellular proliferation, we have proposed that the pharmacological modulation of these signaling pathways could be a new strategy for cancer therapy.

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Meta-Analysis of Public Microarray Datasets Reveals Voltage-Gated Calcium Gene Signatures in Clinical Cancer Patients

Cited by 94 publications

References 137 publications

L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling

L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling

Targeting calcium signaling in cancer therapy

A Novel Alternative for Cancer Therapy: Pharmacological Modulation of Ca2+/cAMP Intracellular Signaling Interaction

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