ArticleScience signaling2015
Phosphorylation of FADD by the kinase CK1α promotes KRASG12D-induced lung cancer.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 48 citations in OpenAlex.
- Targeting casein kinase 1α-mediated FADD phosphorylation restores sensitivity in select CDK4/6 inhibitor-resistant breast cancer models.The Journal of clinical investigation · 2026Article
- Article
- Exploring the role of casein kinase 1α splice variants across cancer cell lines.Biochemical and biophysical research communications · 2024Article
- Modeling Molecular Pathogenesis of Idiopathic Pulmonary Fibrosis-Associated Lung Cancer in Mice.Molecular cancer research : MCR · 2024Article
- Selective CK1α degraders exert antiproliferative activity against a broad range of human cancer cell lines.Nature communications · 2024Article
- The diagnostic or prognostic values of FADD in cancers based on pan‑cancer analysis.Biomedical reports · 2023Article
- Prognostic significance and immune correlates of FADD in penile squamous cell carcinoma.Virchows Archiv : an international journal of pathology · 2023Article
- TRAIL receptors promote constitutive and inducible IL-8 secretion in non-small cell lung carcinoma.Cell death & disease · 2022Article
- A Dual Role for FADD in Human Precursor T-Cell Neoplasms.International journal of molecular sciences · 2022Article
- FADD as a key molecular player in cancer progression.Molecular medicine (Cambridge, Mass.) · 2022Review
- The kinase PLK1 promotes the development ofScience signaling · 2022Article
- Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells.Nutrients · 2022Article
- CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes.Cancers · 2022Review
- The Classical Apoptotic Adaptor FADD Regulates Glycolytic Capacity in Acute Lymphoblastic Leukemia.International journal of biological sciences · 2022Article
- HS3ST1 Promotes Non-Small-Cell Lung Cancer Progression by Targeting the SPOP/FADD/NF-BioMed research international · 2022Article
- Methods to Study Posttranslational Modification Patterns in Cytotoxic T-Cells and Cancer.Methods in molecular biology (Clifton, N.J.) · 2021Article
- The cytochrome P450 enzyme CYP24A1 increases proliferation of mutant KRAS-dependent lung adenocarcinoma independent of its catalytic activity.The Journal of biological chemistry · 2020Article
- Heterogeneous genomic aberrations in esophageal squamous cell carcinoma: a review.American journal of translational research · 2020Review
- Review
- Correlation between CK1α and β-catenin Ser45-phosphorylation in patients with esophageal squamous cell carcinoma.International journal of clinical and experimental pathology · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Genomic amplification of the gene encoding and phosphorylation of the protein FADD (Fas-associated death domain) is associated with poor clinical outcome in lung cancer and in head and neck cancer. Activating mutations in the guanosine triphosphatase RAS promotes cell proliferation in various cancers. Increased abundance of phosphorylated FADD in patient-derived tumor samples predicts poor clinical outcome. Using immunohistochemistry analysis and in vivo imaging of conditional mouse models of KRAS(G12D)-driven lung cancer, we found that the deletion of the gene encoding FADD suppressed tumor growth, reduced the proliferative index of cells, and decreased the activation of downstream effectors of the RAS-MAPK (mitogen-activated protein kinase) pathway that promote the cell cycle, including retinoblastoma (RB) and cyclin D1. In mouse embryonic fibroblasts, the induction of mitosis upon activation of KRAS required FADD and the phosphorylation of FADD by CK1α (casein kinase 1α). Deleting the gene encoding CK1α in KRAS mutant mice abrogated the phosphorylation of FADD and suppressed lung cancer development. Phosphorylated FADD was most abundant during the G2/M phase of the cell cycle, and mass spectrometry revealed that phosphorylated FADD interacted with kinases that mediate the G2/M transition, including PLK1 (Polo-like kinase 1), AURKA (Aurora kinase A), and BUB1 (budding uninhibited by benzimidazoles 1). This interaction was decreased in cells treated with a CKI-7, a CK1α inhibitor. Therefore, as the kinase that phosphorylates FADD downstream of RAS, CK1α may be a therapeutic target for KRAS-driven lung cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.