Phosphorylated FADD induces NF-κB, perturbs cell cycle, and is associated with poor outcome in lung adenocarcinomas

Chen, Guoan; Bhojani, Mahaveer S.; Heaford, Andrew C.; Chang, Daphne; Laxman, Bharathi; Thomas, Dafydd G.; Griffin, Laura B.; Yu, James B.; Coppola, Julia M.; Giordano, Thomas J.; Lin, Lin; Adams, David; Orringer, Mark B.; Ross, Brian D.; Beer, David G.; Rehemtulla, Alnawaz

doi:10.1073/pnas.0500397102

Cited by 121 publications

(175 citation statements)

References 43 publications

Supporting

Mentioning

158

Contrasting

Order By: Relevance

“…Alternatively, Akt may phosphorylate FADD after it has bound to FAS receptor, to hinder recruitment of pro-caspase 8 and c-Flip. While the kinase modifying FADD phosphorylation is yet to be determined, these possibilities are consistent with accumulating evidence suggesting that phosphorylation of FADD functions in controlling pathways of cellular activation and proliferation (Zhang et al, 2004;Chen et al, 2005). These possibilities are subjects of future investigations.…”

Section: Discussionsupporting

confidence: 73%

Phosphatidylinositol 3-kinase/Akt signaling mediates interleukin-6 protection against p53-induced apoptosis in M1 myeloid leukemic cells

2006

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 73%

Phosphatidylinositol 3-kinase/Akt signaling mediates interleukin-6 protection against p53-induced apoptosis in M1 myeloid leukemic cells

2006

View full text Add to dashboard Cite

“…Gene by gene functional analyses have revealed that cyclin D1 (Opitz et al, 2001;Nelsen et al, 2005), FADD (Alappat et al, 2003;Chen et al, 2005) and cortactin (van Rossum et al, 2003;Luo et al, 2006) are potentially able to enhance cancer development. However, these studies do not account for the effect of multiple genes located within the 11q13.3 amplicon.…”

Section: Discussion Cortactin Predicts Poor Survival In Late Stage Lamentioning

confidence: 99%

Cortactin expression predicts poor survival in laryngeal carcinoma

et al. 2008

View full text Add to dashboard Cite

Amplification of the 11q13 region is one of the most frequent aberrations in squamous cell carcinomas of the head and neck region (HNSCC). Amplification of 11q13 has been shown to correlate with the presence of lymph node metastases and decreased survival. The 11q13.3 amplicon carries numerous genes including cyclin D1 and cortactin. Recently, we reported that FADD becomes overexpressed upon amplification and that FADD protein expression predicts for lymph node positivity and disease-specific mortality. However, the gene within the 11q13.3 amplicon responsible for this correlation is yet to be identified. In this paper, we compared, using immunohistochemical analysis for cyclin D1, FADD and cortactin in a series of 106 laryngeal carcinomas which gene correlates best with lymph node metastases and increased disease-specific mortality. Univariate Cox regression analysis revealed that high expression of cyclin D1 (P ¼ 0.016), FADD (P ¼ 0.003) and cortactin (P ¼ 0.0006) predict for increased risk to disease-specific mortality. Multivariate Cox analysis revealed that only high cortactin expression correlates with disease-specific mortality independent of cyclin D1 and/or FADD. Of genes located in the 11q13 amplicon, cortactin expression is the best predictor for shorter diseasespecific survival in late stage laryngeal carcinomas. Current methods to predict the outcome of head and neck squamous cell carcinoma (HNSCC) patients mainly involve clinicopathological parameters such as tumour size, differentiation grade and presence of lymph node metastasis. Patients with laryngeal squamous cell carcinomas (LSCC) have not shown an increase in 5-year survival rates over the last 30 years (Almadori et al, 2005). Therefore, other parameters such as molecular markers that are able to more accurately predict the outcome of disease, are needed.A frequent molecular event in HNSCC is amplification of the 11q13 region (36%) (Schuuring, 1995;Freier et al, 2006). Amplification of this region in HNSCC has been associated with decreased survival (Akervall et al, 1995;Meredith et al, 1995), increased distant metastasis (Namazie et al, 2002) and lymph node metastasis (Chen et al, 2004;Hermsen et al, 2005;Xia et al, 2007). It is believed that amplification increases gene dosage and expression of genes within the amplified region (amplicon) (Albertson, 2006). Recently, we reported that the commonly amplified region is located at 11q13.3 and contains at least six genes (cyclin D1, TAOS1, FGF19, FADD, PPFIA1 and cortactin) that are overexpressed when amplified (Gibcus et al, 2007b). We concluded that the selection for tumour cells with the 11q13.3 amplicon during tumorigenesis could be based on the increased doses of one or more of these genes. We proposed FADD as a possible candidate for this selection, since FADD showed the best correlation between DNA amplification and increased expression (Gibcus et al, 2007b). Furthermore, FADD protein expression correlated with disease specific mortality (DSM) in a series of late stage laryngeal carcinom...

show abstract

“…Moreover, PI3K/Akt-dependent signaling is involved in the activation of NF-kB downstream of Her-2/ErbB2 (Pianetti et al, 2001). Relative to other signaling pathways, in a significant number of lung adenocarcinomas, Fas-associated death domain phosphorylation is associated with poor clinical outcome and induces IKK-mediated NF-kB activation (Chen et al, 2005). Interestingly, in pancreatic cancer cells, high levels of expression of the E3-ubiquitin ligase receptor beta-transducin repeat-containing protein 1 (bTRCP1) is proposed to activate NF-kB (Muerkoster et al, 2005; Figure 2).…”

Section: Activation By Oncoproteinsmentioning

confidence: 99%

Nuclear factor-κB and inhibitor of κB kinase pathways in oncogenic initiation and progression

2006

View full text Add to dashboard Cite

Phosphorylated FADD induces NF-κB, perturbs cell cycle, and is associated with poor outcome in lung adenocarcinomas

Abstract: In an effort to identify a clinical biomarker for lung cancer, we used cDNA microarray and 2D protein analyses to demonstrate that increased Fas-associated death domain (

Cited by 121 publications

References 43 publications

Phosphatidylinositol 3-kinase/Akt signaling mediates interleukin-6 protection against p53-induced apoptosis in M1 myeloid leukemic cells

Phosphatidylinositol 3-kinase/Akt signaling mediates interleukin-6 protection against p53-induced apoptosis in M1 myeloid leukemic cells

Cortactin expression predicts poor survival in laryngeal carcinoma

Nuclear factor-κB and inhibitor of κB kinase pathways in oncogenic initiation and progression

Contact Info

Product

Resources

About