The emerging role of CaMKII in cancer

Wang, Yanyang; Zhao, Ren; Zhe, Hong

doi:10.18632/oncotarget.3955

Cited by 95 publications

(78 citation statements)

References 76 publications

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“…CaMKII holoenzymes contain 8-14 subunits, each with a catalytic domain, a regulatory domain, and an association domain, all organized so that catalytic domains are placed in pairs. [67][68][69][70] Ca 2C /CaM binding to the regulatory domain causes a conformational change that removes the autoinhibitory pseudosubstrate segment from the active site, which allows for ATP binding and also exposes T286 of the autoinhibitory pseudo-substrate segment for phosphorylation. 69,[71][72][73][74][75] This phosphorylation sterically prevents the inhibitory segment from returning to the active site once Ca 2C /CaM has dissociated, resulting in continued activation independent of calcium.…”

Section: Molecular Regulation Of Epithelial Scattering By Calcium/calmentioning

confidence: 99%

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

2016

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Epithelial tissues use adherens junctions to maintain tight interactions and coordinate cellular activities. Adherens junctions are remodeled during epithelial morphogenesis, including instances of epithelialmesenchymal transition, or EMT, wherein individual cells detach from the tissue and migrate as individual cells. EMT has been recapitulated by growth factor induction of epithelial scattering in cell culture. In culture systems, cells undergo a highly reproducible series of cell morphology changes, most notably cell spreading followed by cellular compaction and cell migration. These morphology changes are accompanied by striking actin rearrangements. The current evidence suggests that global changes in actomyosin-based cellular contractility, first a loss of contractility during spreading and its activation during cell compaction, are the main drivers of epithelial scattering. In this review, we focus on how spreading and contractility might be controlled during epithelial scattering. While we propose a central role for RhoA, which is well known to control cellular contractility in multiple systems and whose role in epithelial scattering is well accepted, we suggest potential roles for additional cellular systems whose role in epithelial cell biology has been less well documented. In particular, we propose critical roles for vesicle recycling, calcium channels, and calcium-dependent kinases.

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Section: Molecular Regulation Of Epithelial Scattering By Calcium/calmentioning

confidence: 99%

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

2016

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“…Accumulating evidence has also shown that CaM plays a pivotal role in tumor development. 14,15 In addition, it has been reported that γ isoform of CaMKII (CaMKIIγ) is required for maintenance of stem-like and tumorigenic properties of lung and liver cancer cells. 12,13 Among them, Ca 2+ /CaM-dependent protein kinase II (CaMKII), a serine/threonine kinase, directly or indirectly upregulates multiple signaling pathways, such as extracellular signal-regulated kinase (ERK)1/2, protein kinase B (Akt), signal transducer and activator of transcription 3 (Stat3), and β-catenin, which are responsible for cancer cell proliferation and metastasis.…”

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confidence: 99%

A curcumin derivative hydrazinobenzoylcurcumin suppresses stem‐like features of glioblastoma cells by targeting Ca²⁺/calmodulin‐dependent protein kinase II

Shin

Lee

Jung

2018

J of Cellular Biochemistry

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Glioblastoma multiforme (GBM) is the most aggressive and common type of human primary brain tumor. Glioblastoma stem‐like cells (GSCs) have been proposed to contribute to tumor initiation, progression, recurrence, and therapeutic resistance of GBM. Therefore, targeting GSCs could be a promising strategy to treat this refractory cancer. Calmodulin (CaM), a major regulator of Ca2+‐dependent signaling, controls various cellular functions via interaction with multiple target proteins. Here, we investigated the anticancer effect of hydrazinobenzoylcurcumin (HBC), a Ca 2+/CaM antagonist, against GSCs derived from U87MG and U373MG cells. HBC significantly inhibited not only the self‐renewal capacity, such as cell growth and neurosphere formation but also the metastasis‐promoting ability, such as migration and invasion of GSCs. HBC induced apoptosis of GSCs in a caspase‐dependent manner. Notably, HBC repressed the phosphorylation of Ca 2+/CaM‐dependent protein kinase II (CaMKII), c‐Met, and its downstream signal transduction mediators, thereby reducing the expression levels of GSC markers, such as CD133, Nanog, Sox2, and Oct4. In addition, the knockdown of CaMKIIγ remarkably decreased the cancer stem cell‐like phenotypes as well as the expression of stemness markers by blocking c‐Met signaling pathway in U87MG GSCs. These results suggest that HBC suppresses the stem‐like features of GBM cells via downregulation of CaM/CaMKII/c‐Met axis and therefore CaMKII may be a novel therapeutic target to eliminate GSCs.

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“…AKT1 is involved in cell proliferation and survival [25], while CAMK2D, a member of the CAMK family, activates cancer cell proliferarion [26]. In fact, CRK proteins have been reported to be dysregulated in several human malignancies [27].…”

Section: Discussionmentioning

confidence: 99%

Investigating the mechanism of hepatocellular carcinoma progression by constructing genetic and epigenetic networks using NGS data identification and big database mining method

Chang

Chen

2016

Oncotarget

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The mechanisms leading to the development and progression of hepatocellular carcinoma (HCC) are complicated and regulated genetically and epigenetically. The recent advancement in high-throughput sequencing has facilitated investigations into the role of genetic and epigenetic regulations in hepatocarcinogenesis. Therefore, we used systems biology and big database mining to construct genetic and epigenetic networks (GENs) using the information about mRNA, miRNA, and methylation profiles of HCC patients. Our approach involves analyzing gene regulatory networks (GRNs), protein-protein networks (PPINs), and epigenetic networks at different stages of hepatocarcinogenesis. The core GENs, influencing each stage of HCC, were extracted via principal network projection (PNP). The pathways during different stages of HCC were compared. We observed that extracellular signals were further transduced to transcription factors (TFs), resulting in the aberrant regulation of their target genes, in turn inducing mechanisms that are responsible for HCC progression, including cell proliferation, anti-apoptosis, aberrant cell cycle, cell survival, and metastasis. We also selected potential multiple drugs specific to prominent epigenetic network markers of each stage of HCC: lestaurtinib, dinaciclib, and perifosine against the NTRK2, MYC, and AKT1 markers influencing HCC progression from stage I to stage II; celecoxib, axitinib, and vinblastine against the DDIT3, PDGFB, and JUN markers influencing HCC progression from stage II to stage III; and atiprimod, celastrol, and bortezomib against STAT3, IL1B, and NFKB1 markers influencing HCC progression from stage III to stage IV.

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The emerging role of CaMKII in cancer

Cited by 95 publications

References 76 publications

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

A curcumin derivative hydrazinobenzoylcurcumin suppresses stem‐like features of glioblastoma cells by targeting Ca²⁺/calmodulin‐dependent protein kinase II

Investigating the mechanism of hepatocellular carcinoma progression by constructing genetic and epigenetic networks using NGS data identification and big database mining method

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The emerging role of CaMKII in cancer

Cited by 95 publications

References 76 publications

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

A curcumin derivative hydrazinobenzoylcurcumin suppresses stem‐like features of glioblastoma cells by targeting Ca2+/calmodulin‐dependent protein kinase II

Investigating the mechanism of hepatocellular carcinoma progression by constructing genetic and epigenetic networks using NGS data identification and big database mining method

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A curcumin derivative hydrazinobenzoylcurcumin suppresses stem‐like features of glioblastoma cells by targeting Ca²⁺/calmodulin‐dependent protein kinase II