ArticleScientific reports2018
The tyrosine phosphorylated pro-survival form of Fas intensifies the EGF-induced signal in colorectal cancer cells through the nuclear EGFR/STAT3-mediated pathway.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- FAS mediates apoptosis, inflammation, and treatment of pathogen infection.Frontiers in cellular and infection microbiology · 2025Review
- Cervical Cancer Cells Use the CD95 and IL-2 Pathways to Promote Their Proliferation and Survival.Biomolecules · 2024Article
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- FIP-nha, a fungal immunomodulatory protein fromFood chemistry. Molecular sciences · 2022Article
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- Therapeutic approaches targeting CD95L/CD95 signaling in cancer and autoimmune diseases.Cell death & disease · 2022Review
- Molecular Targets and Mechanisms ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
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- MiR-30a-5p inhibits proliferation and metastasis of hydatidiform mole by regulating B3GNT5 through ERK/AKT pathways.Journal of cellular and molecular medicine · 2020Article
- Downregulation of thioredoxin-1-dependent CD95 S-nitrosation by Sorafenib reduces liver cancer.Redox biology · 2020Article
- A quantitative trait locus on chromosome 2 was identified that accounts for a substantial proportion of phenotypic variance of the yellow plumage color in chicken.Poultry science · 2020Article
- Calcitonin gene-related peptide inhibits angiotensin II-induced NADPH oxidase-dependent ROS via the Src/STAT3 signalling pathway.Journal of cellular and molecular medicine · 2020Article
- Review
- Sodium cantharidate targets STAT3 and abrogates EGFR inhibitor resistance in osteosarcoma.Aging · 2019Article
- Comprehensive analysis of competing endogenous RNA network and 3-mRNA signature predicting survival in papillary renal cell cancer.Medicine · 2019Observational
- EGFR deficiency leads to impaired self-renewal and pluripotency of mouse embryonic stem cells.PeerJ · 2019Article
- The natural polyphenol curcumin induces apoptosis by suppressing STAT3 signaling in esophageal squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine phosphorylation of Fas (TNFRSF6/CD95) in its death domain turns off Fas-mediated apoptosis, turns on the pro-survival signal, and has implications in different cancers types. We show here that Fas in its pro-survival state, phosphorylated at Y291 (pY291-Fas), functionally interacts with the epidermal growth factor receptor (EGFR), a key cancer-driving protein and major therapeutic target. Using an evolution-guided pY291-Fas proxy, RNA interference, and site-specific phospho-protein detection, we show that pY291-Fas significantly intensifies EGFR signaling in anti-EGFR-resistant colorectal cancer cells via the Yes-1/STAT3-mediated pathway. The pY291-Fas is essential for the EGF-induced formation of the Fas-mediated nuclear EGFR/STAT3 signaling complex consisting of Fas, EGFR, Yes-1, Src, and STAT3. The pY291-Fas accumulates in the nucleus upon EGF treatment and promotes the nuclear localization of phospho-EGFR and phospho-STAT3, the expression of cyclin D1, the activation of STAT3-mediated Akt and MAPK pathways, and cell proliferation and migration. This novel cancer-promoting function of phosphorylated Fas in the nuclear EGFR signaling constitutes the foundation for developing pro-survival-Fas targeted anti-cancer therapies to overcome disease recurrence in patients with anti-EGFR resistant cancer.
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