Increased expression of Mcl‐1 is responsible for the blockage of TRAIL‐induced apoptosis mediated by EGF/ErbB1 signaling pathway

Henson, Elizabeth S.; Gibson, Erika M; Villanueva, Jacylyn; Bristow, Nicolle; Haney, Neil; Gibson, Spencer B.

doi:10.1002/jcb.10597

Cited by 62 publications

(61 citation statements)

References 41 publications

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“…Therefore, our data show that P. aeruginosa mucoid strains, which chronically infect CF patients, do not elicit the expression of proinflammatory pathways in this model of airway epithelial cells. Interestingly, our microarray analysis showed FRD1-dependent up-regulation of genes with antiapoptotic effect on epithelial and other cell types (63)(64)(65), and exposure to an alginate-producing strain results in diminished apoptosis in Calu-3 airway epithelial cells. Thus, the lack of the appropriate host defense and inflammatory milieu in the airways, and impaired bacterial clearance because of reduced epithelial cell apoptosis (59,66), may explain the increased persistence of these strains in animal models of acute infection (15)(16)(17)(18).…”

Section: Discussionmentioning

confidence: 83%

Pseudomonas aeruginosa Flagellin and Alginate Elicit Very Distinct Gene Expression Patterns in Airway Epithelial Cells: Implications for Cystic Fibrosis Disease

Cobb

Mychaleckyj

Wozniak

et al. 2004

The Journal of Immunology

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Infection with the opportunistic pathogen Pseudomonas aeruginosa remains a major health concern. Two P. aeruginosa phenotypes relevant in human disease include motility and mucoidy. Motility is characterized by the presence of flagella and is essential in the establishment of acute infections, while mucoidy, defined by the production of the exopolysaccharide alginate, is critical in the development of chronic infections, such as the infections seen in cystic fibrosis patients. Indeed, chronic infection of the lung by mucoid P. aeruginosa is a major cause of morbidity and mortality in cystic fibrosis patients. We have used Calu-3 human airway epithelial cells to investigate global responses to infection with motile and mucoid P. aeruginosa. The response of airway epithelial cells to exposure to P. aeruginosa motile strains is characterized by a specific increase in gene expression in pathways controlling inflammation and host defense. By contrast, the response of airway epithelia to the stimuli presented by mucoid P. aeruginosa is not proinflammatory and, hence, may not be conducive to the effective elimination of the pathogen. The pattern of gene expression directed by flagellin, but not alginate, includes innate host defense genes, proinflammatory cytokines, and chemokines. By contrast, infection with alginate-producing P. aeruginosa results in an overall attenuation of host responses and an antiapoptotic effect.

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Section: Discussionmentioning

confidence: 83%

Pseudomonas aeruginosa Flagellin and Alginate Elicit Very Distinct Gene Expression Patterns in Airway Epithelial Cells: Implications for Cystic Fibrosis Disease

Cobb

Mychaleckyj

Wozniak

et al. 2004

The Journal of Immunology

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“…In zebrafish embryos, knockdown of zMcl1a and zMcl-1b substantially increased apoptosis triggered by ectopic expression of the Apo2L/TRAIL homolog zDL1b. Previous work suggests that in human hepatocellular carcinoma-derived cells, 32 human cholangiocarcinoma cells, 31 and NIH3T3 mouse fibroblasts, 30 Mcl-1 is a critical modulator of sensitivity to apoptosis signaling by Apo2L/TRAIL. Hence, endogenous Mcl-1 may be particularly important among prosurvival Bcl-2 family members in controlling apoptosis induction by stimuli that engage both the extrinsic and intrinsic apoptosis pathways.…”

Section: Discussionmentioning

confidence: 99%

“…[30][31][32] Thus, Mcl-1 may be a key modulator of DLinduced apoptosis in cells that require engagement of both the extrinsic and intrinsic pathways for commitment to apoptosis. Furthermore, these results indicate that endogenous zMcl-1a and zMcl-1b play an important role in curtailing apoptosis induction through the cell-intrinsic pathway in early zebrafish embryos.…”

Section: Apo2l/trailmentioning

confidence: 99%

Functional characterization of the Bcl-2 gene family in the zebrafish

Kratz

Eimon

Mukhyala³

et al. 2006

Cell Death Differ

128

155

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Members of the Bcl-2 protein family control the intrinsic apoptosis pathway. To evaluate the importance of this family in vertebrate development, we investigated it in the zebrafish (Danio rerio). We found that the zebrafish genome encodes structural and functional homologs of most mammalian Bcl-2 family members, including multi-Bcl-2-homology (BH) domain proteins and BH3-only proteins. Apoptosis induction by c-irradiation required zBax1 and zPuma, and could be prevented by overexpression of homologs of prosurvival Bcl-2 family members. Surprisingly, zebrafish Bax2 (zBax2) was homologous to mammalian Bax by sequence and synteny, yet demonstrated functional conservation with human Bak. Morpholino knockdown of both zMcl-1a and zMcl-1b revealed their critical role in early embryonic zebrafish development, and in the modulation of apoptosis activation through the extrinsic pathway. These data indicate substantial functional similarity between zebrafish and mammalian Bcl-2 family members, and establish the zebrafish as a relevant model for studying the intrinsic apoptosis pathway.

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“…41 There is mounting evidence that Mcl-1 may play an important role in regulating TRAIL-induced apoptosis in cancer cells by antagonizing proapoptotic Bcl-2 family members. [42][43][44][45][46] Furthermore, our findings demonstrate for the first time that neutralizing Mcl-1 is also an effective strategy to enhance the sensitivity of neuroblastoma cells to CD95-or chemotherapy-induced apoptosis. Thus, targeting the TRAIL/NF-jB/Mcl-1 axis in neuroblastoma cells, for example, by small molecule NF-jB inhibitors, may present a promising strategy to enhance the antitumor activity of TRAIL.…”

Section: Sensitization For Trail-induced Apoptosis By Nf-jb Inhibitionmentioning

confidence: 94%

Sensitization of neuroblastoma cells for TRAIL‐induced apoptosis by NF‐κB inhibition

Ammann

Haag

Kasperczyk

et al. 2008

Intl Journal of Cancer

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The transcription factor nuclear factor‐kappaB (NF‐κB) plays a central role in stress‐induced transcriptional activation and has been implicated in chemoresistance of cancers. In the present study, we investigated the role of NF‐κB in inducible chemoresistance of neuroblastoma. Doxorubicin, VP16 and the cytotoxic ligand TRAIL trigger NF‐κB activation, whereas cisplatin and taxol have no impact on NF‐κB activity. Specific inhibition of NF‐κB activation by overexpression of dominant‐negative mutant IκBα‐super‐repressor does not alter cell death upon doxorubicin or VP16 treatment, although it prevents doxorubicin‐ or VP16‐mediated NF‐κB activation. By comparison, inhibition of TRAIL‐stimulated NF‐κB activation by IκBα‐superrepressor or the small molecule NF‐κB inhibitor BMS‐345541 significantly enhances TRAIL‐induced apoptosis, pointing to an antiapoptotic function of NF‐κB in TRAIL‐mediated apoptosis. Analysis of signaling pathways reveals that NF‐κB inhibition prevents TRAIL‐triggered up‐regulation of Mcl‐1, promoting TRAIL‐induced cytochrome c release and activation of caspases. Accordingly, knockdown of Mcl‐1 by RNA interference significantly enhances TRAIL‐induced apoptosis and also increases sensitivity of neuroblastoma cells to CD95‐ or chemotherapy‐induced apoptosis. In conclusion, NF‐κB regulates apoptosis in a stimulus‐specific manner in neuroblastoma cells and confers protection against TRAIL‐induced apoptosis. By demonstrating that NF‐κB inhibition sensitizes neuroblastoma cells for TRAIL‐induced apoptosis, our findings have important implications. Thus, NF‐κB inhibitors may open new perspectives to potentiate the efficacy of TRAIL‐based protocols in the treatment of neuroblastoma. © 2008 Wiley‐Liss, Inc.

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Increased expression of Mcl‐1 is responsible for the blockage of TRAIL‐induced apoptosis mediated by EGF/ErbB1 signaling pathway

Cited by 62 publications

References 41 publications

Pseudomonas aeruginosa Flagellin and Alginate Elicit Very Distinct Gene Expression Patterns in Airway Epithelial Cells: Implications for Cystic Fibrosis Disease

Pseudomonas aeruginosa Flagellin and Alginate Elicit Very Distinct Gene Expression Patterns in Airway Epithelial Cells: Implications for Cystic Fibrosis Disease

Functional characterization of the Bcl-2 gene family in the zebrafish

Sensitization of neuroblastoma cells for TRAIL‐induced apoptosis by NF‐κB inhibition

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