Promoter methylation of DAP-kinase: association with advanced stage in non-small cell lung cancer

Kim, Duk Hwan; Nelson, Heather H.; Wiencke, John K.; Christiani, David C.; Wain, John C.; Mark, Eugene J.; Kelsey, Karl T.

doi:10.1038/sj.onc.1204302

Cited by 138 publications

(112 citation statements)

References 22 publications

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“…DAPK is absent in highly metastatic variants of mouse lung cancer cell lines, and is present in the low metastatic variants of those same cell lines (Inbal et al, 1997). In lung and head and neck cancers, DAPK promoter methylation was associated with aggressive disease and poor survival (Sanchez-Cespedes A new paradigm in cell signaling and cancer therapy D Goldschneider and P Mehlen et al, 2000;Tang et al, 2000;Kim et al, 2001;Kong et al, 2005). DRAL was initially characterized as a downregulated gene in rhabdomyosarcoma (Genini et al, 1997).…”

Section: Drs Are Altered During Tumor Progressionmentioning

confidence: 99%

Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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Dependence receptors (DRs) now form a family of more than a dozen membrane receptors that are not linked by their structure, but by common functional traits. The most notable is their ability to trigger two opposite signaling pathways: in the presence of ligand, these receptors activate classic signaling pathways implicated in cell survival, migration and differentiation. In the absence of ligand, they do not stay inactive, rather they elicit an apoptotic signal. Thus, cells expressing this kind of receptor are dependent on the presence of ligand in the extracellular environment to survive. This review will recapitulate the increasing data regarding the molecular mechanisms associated with DRs, their potential implication during development, as well as their deregulation during tumorigenesis and, finally, their emergence as new possible therapeutic targets for cancer treatment.

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Section: Drs Are Altered During Tumor Progressionmentioning

confidence: 99%

Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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“…In lung cancers, DAPk promoter methylation was associated with aggressive disease and poor survival. [35][36][37][38] Lung tumors that were positive for DAPk hypermethylation showed advanced pathological stage, larger tumor size and lymph node involvement. 35 Similarly, DAPk hypermethylation in head and neck cancer correlated with lymph node involvement and advanced disease stage.…”

Section: Dapk Family and Cancer: A Novel Tumor Suppressor Family Of Pmentioning

confidence: 99%

“…[35][36][37][38] Lung tumors that were positive for DAPk hypermethylation showed advanced pathological stage, larger tumor size and lymph node involvement. 35 Similarly, DAPk hypermethylation in head and neck cancer correlated with lymph node involvement and advanced disease stage. 39,40 Analysis of oligodendroglioma samples showed that the DAPk hypermethylation rate increased in parallel with the grade of malignancy of these tumors.…”

Section: Dapk Family and Cancer: A Novel Tumor Suppressor Family Of Pmentioning

confidence: 99%

DAPk Protein Family and Cancer

Gözüaçık¹,

Kimchi²

2006

Autophagy

191

172

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The Death-Associated Protein kinase (DAPk) family contains three closely related serine/threonine kinases, named DAPk, ZIPk and DRP-1, which display a high degree of homology in their catalytic domains. The recent discovery of protein-protein interactions and kinase/substrate relationships among these family members suggests that the three kinases may form multi-protein complexes capable of transmitting apoptotic or autophagic cell death signals in response to various cellular stresses including the misregulated expression of oncogenes in premalignant cells. Several lines of evidence indicate that the most studied member of the family, DAPk, has tumor and metastasis suppressor properties. Here we present an overview of the data connecting the DAPk family of proteins to cell death and malignant transformation and discuss the possible involvement of the autophagic cell death-inducing capacity of DAPk in its tumor suppressor activity.

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“…[15][16][17][18][19] In some cases, reduced expression levels have been correlated with metastatic progression, disease recurrence, and unfavorable prognosis. 18,[20][21][22] Despite its critical role as a tumor suppressor, little is known about the direct molecular mechanisms by which DAPk causes cell death. Catalytic activity is required for its deathinducing capabilities, 1 yet DAPk's in vivo substrates have not been identified.…”

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confidence: 99%

DAP-kinase-mediated morphological changes are localization dependent and involve myosin-II phosphorylation

2004

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DAP-kinase (DAPk) is a Ser/Thr kinase that regulates cytoplasmic changes associated with programmed cell death. It is shown here that a GFP-DAPk fusion, which partially localized to actin stress fibers, induced extensive membrane protrusions. This phenotype correlated with changes in myosin-II distribution and with increased phosphorylation of the myosin-II regulatory light chain (RLC). A mutant lacking the cytoskeletal-interacting region (GFP-DAPkDCyto) displayed diffuse cytoplasmic localization, and induced peripheral membrane blebbing, instead of the extensive protrusions. In contrast, deletion of the ankyrin repeats led to mislocalization of the kinase to focal contacts, where it failed to elicit any changes in cell morphology. While both wild-type DAPk and DAPkDCyto induced RLC phosphorylation independently of the Rho-activated kinase ROCK, only the wild type led to increases in stress-fiber associated phospho-RLC. Thus, the precise intracellular localization of DAPk is critical for exposure to its substrates, including the RLC, which mediate varying morphologic changes.

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Promoter methylation of DAP-kinase: association with advanced stage in non-small cell lung cancer

Cited by 138 publications

References 22 publications

Dependence receptors: a new paradigm in cell signaling and cancer therapy

Dependence receptors: a new paradigm in cell signaling and cancer therapy

DAPk Protein Family and Cancer

DAP-kinase-mediated morphological changes are localization dependent and involve myosin-II phosphorylation

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