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Updated: Aug 15, 2026

The Soft Agar Colony Formation Assay
Published on: October 27, 2014
Nuclear localized phosphorylated FADD induces cell proliferation and is associated with aggressive lung cancer
Mahaveer S Bhojani1, Guoan Chen, Brian D Ross
1Department of Radiology, University of Michigan, Ann Arbor, Michigan 48109-0648, USA.
Abstract:
Fas-associated death domain (FADD)/Mort1 was initially reported as a pro-apoptotic adaptor molecule that recruits the initiator caspases 8 and 10 to promote formation of the death-inducing signal complex (DISC) and mediates receptor induced apoptosis. Recent studies have brought to light ancillary death receptor induced apoptosis-independent activities of FADD that include cell cycle regulation, NF-kappaB activation, cell proliferation and role during embryonic development. We have recently shown that in lung adenocarcinomas increased FADD mRNA and protein are significantly associated with poor survival and that FADD overexpression was not due to gene amplification and/or mutation. In this study we showed that the nuclear localization of FADD and elevated expression of the phosphorylated form of FADD (p-FADD) correlated most closely with an increase in NF-kB activity and poor clinical outcome. These results suggest that levels of p-FADD may be used as a prognostic biomarker for predicting survival of lung cancer patients.
Insights
Phosphorylated FADD (p-FADD) in lung cancer cells is linked to increased NF-kB activity and poor survival. Elevated p-FADD levels may serve as a prognostic biomarker for lung cancer patients.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Fas-associated death domain (FADD) is known as a pro-apoptotic adaptor molecule.
- Recent research highlights apoptosis-independent roles of FADD in cell cycle, proliferation, and NF-kB activation.
- FADD overexpression in lung adenocarcinoma correlates with poor survival, independent of gene amplification or mutation.
Purpose of the Study:
- To investigate the correlation between FADD localization, phosphorylation, NF-kB activity, and clinical outcome in lung cancer.
- To evaluate the potential of phosphorylated FADD (p-FADD) as a prognostic biomarker.
Main Methods:
- Analysis of FADD mRNA and protein levels in lung adenocarcinomas.
- Assessment of FADD nuclear localization and phosphorylated FADD (p-FADD) expression.
- Correlation analysis with NF-kB activity and patient survival data.
Main Results:
- Increased FADD mRNA and protein levels are associated with poor survival in lung adenocarcinoma.
- Nuclear localization of FADD and elevated p-FADD expression closely correlate with increased NF-kB activity.
- Both nuclear FADD and elevated p-FADD correlate with poor clinical outcomes.
Conclusions:
- Elevated nuclear FADD and p-FADD expression are linked to increased NF-kB activity and poor prognosis in lung cancer.
- p-FADD levels show potential as a reliable prognostic biomarker for predicting lung cancer patient survival.
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