Calcium/Calmodulin-Dependent Protein Kinase II and Its Endogenous Inhibitor α in Medullary Thyroid Cancer

Russo, Eleonora; Salzano, Marcella; Falco, Valentina De; Mian, Caterina; Barollo, Susi; Secondo, Agnese; Bifulco, Maurizio; Vitale, Mario

doi:10.1158/1078-0432.ccr-13-1683

Cited by 16 publications

(15 citation statements)

References 31 publications

(38 reference statements)

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“…ERK is one of the targets of CaMKII and the CaMKII-ERK cascade has been identified in a recent study (19). Furthermore, a previous study demonstrated that the CaMKII-mediated activation of ERK contributed to cell proliferation of papillary thyroid carcinoma (20).…”

Section: Discussionmentioning

confidence: 99%

Insufficient radiofrequency ablation promotes human hepatoma SMMC7721 cell proliferation by stimulating vascular endothelial growth factor overexpression

et al. 2015

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The aims of the current study were to investigate the influence of insufficient radiofrequency ablation (RFA) on the cell proliferation of the human hepatocellular carcinoma (HCC) cells, SMMC7721, and to elucidate the underlying mechanism. SMMC7721 cells were subjected to a 47°C treatment regimen to simulate insufficient RFA, in the presence or absence of KN93 [a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII)], PD98059 [a specific inhibitor of extracellular signal-regulated kinase (ERK)], or axitinib (a specific inhibitor of vascular endothelial growth factor (VEGF) receptor]. Cell proliferation was determined using a thiazolyl terazolium assay (MTT). The levels of CaMKII, phospho-CaMKII, ERK, phospho-ERK and VEGF were observed by western blot analysis. The results demonstrated that the 47°C treatment regimen: i) Triggered upregulation of VEGF expression in the SMMC7721 cells, which was reduced by CaMKII or ERK inhibition; ii) induced ERK activation was prevented by KN93; and iii) promoted SMMC7721 cell proliferation, which was greatly inhibited by axitinib, KN93 and PD98059. In conclusion, the results indicated that insufficient RFA promotes SMMC7721 cell proliferation by activating CaMKII/ERK-dependent VEGF overexpression.

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Section: Discussionmentioning

confidence: 99%

Insufficient radiofrequency ablation promotes human hepatoma SMMC7721 cell proliferation by stimulating vascular endothelial growth factor overexpression

et al. 2015

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“…The expression of the physiological inhibitor-α of CaMK-II in primary medullary thyroid carcinoma cells inversely correlates with the capacity to form lymph node metastasis [234]. In human follicular thyroid cancer cells Ca 2+ entry via TRPC1 (transient receptor potential channel 1) appears to be important for migration and invasiveness.…”

Section: Cam-dependent Protein Kinasesmentioning

confidence: 99%

The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis

Villalobo

Berchtold

2020

IJMS

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Calmodulin (CaM) is the principal Ca2+ sensor protein in all eukaryotic cells, that upon binding to target proteins transduces signals encoded by global or subcellular-specific changes of Ca2+ concentration within the cell. The Ca2+/CaM complex as well as Ca2+-free CaM modulate the activity of a vast number of enzymes, channels, signaling, adaptor and structural proteins, and hence the functionality of implicated signaling pathways, which control multiple cellular functions. A basic and important cellular function controlled by CaM in various ways is cell motility. Here we discuss the role of CaM-dependent systems involved in cell migration, tumor cell invasiveness, and metastasis development. Emphasis is given to phosphorylation/dephosphorylation events catalyzed by myosin light-chain kinase, CaM-dependent kinase-II, as well as other CaM-dependent kinases, and the CaM-dependent phosphatase calcineurin. In addition, the role of the CaM-regulated small GTPases Rac1 and Cdc42 (cell division cycle protein 42) as well as CaM-binding adaptor/scaffold proteins such as Grb7 (growth factor receptor bound protein 7), IQGAP (IQ motif containing GTPase activating protein) and AKAP12 (A kinase anchoring protein 12) will be reviewed. CaM-regulated mechanisms in cancer cells responsible for their greater migratory capacity compared to non-malignant cells, invasion of adjacent normal tissues and their systemic dissemination will be discussed, including closely linked processes such as the epithelial–mesenchymal transition and the activation of metalloproteases. This review covers as well the role of CaM in establishing metastatic foci in distant organs. Finally, the use of CaM antagonists and other blocking techniques to downregulate CaM-dependent systems aimed at preventing cancer cell invasiveness and metastasis development will be outlined.

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“…32 Using RT-PCR (reverse transcription polymerase chain reaction) confirmed that no mRNA of the blocked calmodulin was transcribed after application of RNAi. The activated calmodulin was found to stimulate an adenylyl cyclase as indicated by inhibitor studies with indomethacine as well as several calmodulin blockers 37 all of which block gravitaxis in Euglena . In contrast, forskulin activates the adenylyl cyclase 38 and augments gravitaxis.…”

Section: Introductionmentioning

confidence: 99%

Gravireceptors in eukaryotes—a comparison of case studies on the cellular level

et al. 2017

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We have selected five evolutionary very different biological systems ranging from unicellular protists via algae and higher plants to human cells showing responses to the gravity vector of the Earth in order to compare their graviperception mechanisms. All these systems use a mass, which may either by a heavy statolith or the whole content of the cell heavier than the surrounding medium to operate on a gravireceptor either by exerting pressure or by pulling on a cytoskeletal element. In many cases the receptor seems to be a mechanosensitive ion channel activated by the gravitational force which allows a gated ion flux across the membrane when activated. This has been identified in many systems to be a calcium current, which in turn activates subsequent elements of the sensory transduction chain, such as calmodulin, which in turn results in the activation of ubiquitous enzymes, gene expression activation or silencing. Naturally, the subsequent responses to the gravity stimulus differ widely between the systems ranging from orientational movement and directed growth to physiological reactions and adaptation to the environmental conditions.

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Calcium/Calmodulin-Dependent Protein Kinase II and Its Endogenous Inhibitor α in Medullary Thyroid Cancer

Cited by 16 publications

References 31 publications

Insufficient radiofrequency ablation promotes human hepatoma SMMC7721 cell proliferation by stimulating vascular endothelial growth factor overexpression

Insufficient radiofrequency ablation promotes human hepatoma SMMC7721 cell proliferation by stimulating vascular endothelial growth factor overexpression

The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis

Gravireceptors in eukaryotes—a comparison of case studies on the cellular level

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