Association of Elevated Protein Kinase CK2 Activity with Aggressive Behavior of Squamous Cell Carcinoma of the Head and Neck

Gapany, M.; Faust, Russell A.; Tawfic, Sherif; Davis, Alan T.; Adams, George L.; Leder, Philip; Ahmed, Khalil

doi:10.1007/bf03401606

Cited by 107 publications

(102 citation statements)

References 19 publications

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“…CK2 may also promote transactivation by phosphorylation of the RelA subunit of NF-nB (17,18). CK2 is overexpressed and activated in HNSCC cell lines and tumor specimens and associated with poor prognosis (19,20). Furthermore, antisense RNA targeting CK2a was found to inhibit proliferation of a HNSCC cell line (21), similar to our findings with inhibition of NF-nB.…”

Section: Introductionsupporting

confidence: 88%

Protein Kinase Casein Kinase 2 Mediates Inhibitor-κB Kinase and Aberrant Nuclear Factor-κB Activation by Serum Factor(s) in Head and Neck Squamous Carcinoma Cells

Yeh²,

Waes³

2006

Cancer Research

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We showed previously that the signal transcription factor nuclear factor-KB (NF-KB) is aberrantly activated and that inhibition of NF-KB induces cell death and inhibits tumorigenesis in head and neck squamous cell carcinomas (HNSCC). Thus, identification of specific kinases underlying the activation of NF-KB could provide targets for selective therapy. Inhibitor-KB (IKB) kinase (IKK) is known to activate NF-KB by inducing NH 2 -terminal phosphorylation and degradation of its endogenous inhibitor, IKB. Casein kinase 2 (CK2) was previously reported to be overexpressed in HNSCC cells and to be a COOH-terminal IKK, but its relationship to NF-KB activation in HNSCC cells is unknown. In this study, we examined the contribution of IKK and CK2 in the regulation of NF-KB in HNSCC in vitro. NF-KB activation was specifically inhibited by kinase-dead mutants of the IKK1 and IKK2 subunits or small interfering RNA targeting the B subunit of CK2. CK2 and IKK kinase activity, as well as NF-KB transcriptional activity, was shown to be serum responsive, indicating that these kinases mediate aberrant activation of NF-KB in response to serum factor(s) in vitro. Recombinant CK2A was shown to phosphorylate recombinant IKK2 as well as to promote immunoprecipitated IKK complex from HNSCC to phosphorylate the NH 2 -terminal S32/S36 of IKBA. We conclude that the aberrant NF-KB activity in HNSCC cells in response to serum is partially through a novel mechanism involving CK2-mediated activation of IKK2, making these kinases candidates for selective therapy to target the NF-KB pathway in HNSCC.

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Section: Introductionsupporting

confidence: 88%

Protein Kinase Casein Kinase 2 Mediates Inhibitor-κB Kinase and Aberrant Nuclear Factor-κB Activation by Serum Factor(s) in Head and Neck Squamous Carcinoma Cells

Yeh²,

Waes³

2006

Cancer Research

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“…CK2 activity is elevated in embryonic tissues as well as in human cancer cells including leukemias and solid tumors (Daya-Makin et al, 1994;Faust et al, 1996;Friedrich and Ingram, 1989;Gapany et al, 1995;Issinger, 1993;Mestres et al, 1994;Munstermann et al, 1990). This elevated activity in rapidly dividing cells suggests an important role for CK2 in the regulation of cellular proliferation, and we have directly demonstrated its critical role in the pathogenesis of cancer by over-expressing the a catalytic subunit in lymphocytes of transgenic mice (Seldin and Leder, 1995).…”

Section: Introductionmentioning

confidence: 58%

p53 deficiency and misexpression of protein kinase CK2α collaborate in the development of thymic lymphomas in mice

et al. 1998

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Protein kinase CK2 (casein kinase II) is a serinethreonine protein kinase with many substrates, some of which are involved in cell cycle regulation. CK2 activity is elevated in human solid tumors and leukemia, and dysregulated expression of CK2 induces lymphoma in transgenic mice. Mice that are de®cient in p53 also develop lymphomas, and p53 activity may be regulated by CK2 phosphorylation. Here we demonstrate that CK2a transgenic mice partially or completely de®cient in p53 develop thymic lymphomas at a markedly accelerated rate when compared to p53-de®cient mice lacking the transgene. Lymphomas originating from CK2a transgenic mice that are heterozygous for p53 generally lose the wild type p53 allele, indicating that loss of p53 is an important step in tumor progression. Moreover, though lymphomas occur as early as 3 weeks of age in the transgenic mice that are nullizygous for p53, they are still monoclonal, indicating that additional stochastic mutations are required for their development. These lymphomas express high levels of myc mRNA and frequently ectopically express Lmo-2, a transcription factor involved in human T cell acute lymphocytic leukemia. The p53-null CK2a transgenic lymphomas grow rapidly but are highly prone to apoptosis, suggesting that transformation occurs through synergistic dysregulation of cell cycle control induced by misexpression of CK2 and loss of function of p53.

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“…Experimental transgenic mouse models of neoplasia in which altered CK2 signal served as a double transgene have provided significant support to this notion (e.g., Kelliher et al, 1996;Xu et al, 1999). The presence of elevated CK2 in cancer appears to correlate with the pathological status of the cancer and may serve as a prognostic marker (Yenice et al, 1994;Gapany et al, 1995;Faust et al, 1996;Faust et al, 1999;Piazza et al, 2006;Laramas et al, 2007). Although CK2 is present ubiquitously in all cells, it is noteworthy that its distribution in the normal versus cancer cells is distinct.…”

Section: Ck2 and Cancermentioning

confidence: 98%

Protein kinase CK2 – A key suppressor of apoptosis

Ahmad

Wang

Unger

et al. 2008

Advances in Enzyme Regulation

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233

188

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Association of Elevated Protein Kinase CK2 Activity with Aggressive Behavior of Squamous Cell Carcinoma of the Head and Neck

Cited by 107 publications

References 19 publications

Protein Kinase Casein Kinase 2 Mediates Inhibitor-κB Kinase and Aberrant Nuclear Factor-κB Activation by Serum Factor(s) in Head and Neck Squamous Carcinoma Cells

Protein Kinase Casein Kinase 2 Mediates Inhibitor-κB Kinase and Aberrant Nuclear Factor-κB Activation by Serum Factor(s) in Head and Neck Squamous Carcinoma Cells

p53 deficiency and misexpression of protein kinase CK2α collaborate in the development of thymic lymphomas in mice

Protein kinase CK2 – A key suppressor of apoptosis

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