Non-small cell lung cancer (WP4255)
Homo sapiens
Non-small cell lung cancer (NSCLC) represents 85% of lung cancer and is defined as any type of epithelial lung cancer that is NOT small cell carcinoma, including squamous cell (SCC), adeno (AC) and large-cell carcinoma. Mutations in NSCLC: * KRAS (mutated in ~29% of NSCLC patients) inactivates its GTPase activity and the p21-RAS protein continuously transmits growth signals to the nucleus. * Mutations or overexpression of EGFR (~22% of NSCLC patients) leads to increased proliferation. * The abnormal fusion of EML4-ALK (~5% of NSCLC patients) leads to constitutive ALK activation, which causes cell proliferation, invasion, and inhibition of apoptosis. * Inactivating mutation of p53 (~50% of NSCLC patients) leads to reduced apoptosis and proliferation. * The protein encoded by the p16INK4a, CDKN2A, inhibits formation of CDK-cyclin-D complexes by competitive binding of CDK4 and CDK6. p16INK4a is mutated in ~12% of NSCLC patients, which leads to a loss of this inhibitory effect. * RARB is a nuclear retinoic acid receptor whose function is often lost in NSCLC, leading to a loss of cell growth control. This pathway was developed based on https://www.kegg.jp/dbget-bin/www_bget?pathway+map05223. Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.
Authors
Kristina Hanspers , Alex Pico , Egon Willighagen , Friederike Ehrhart , and Finterly HuActivity
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Cited In
- Precision Oncology: Artificial Intelligence and DNA Methylation Analysis of Circulating Cell-Free DNA for Lung Cancer Detection (2022).
- Shared mechanisms and crosstalk of COVID-19 and osteoporosis via vitamin D (2022).
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Organisms
Homo sapiensCommunities
CPTAC DiseasesAnnotations
Pathway Ontology
lung cancer pathway disease pathway cancer pathwayDisease Ontology
lung cancerCell Type Ontology
bronchial epithelial cellReferences
- KEGG Pathway: map05223
- Induction of apoptosis by tumor suppressor FHIT via death receptor signaling pathway in human lung cancer cells. Deng WG, Nishizaki M, Fang B, Roth JA, Ji L. Biochem Biophys Res Commun. 2007 Apr 20;355(4):993–9. PubMed Europe PMC Scholia
- The biology and treatment of EML4-ALK non-small cell lung cancer. Sasaki T, Rodig SJ, Chirieac LR, Jänne PA. Eur J Cancer. 2010 Jul;46(10):1773–80. PubMed Europe PMC Scholia
- Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment. Connolly RM, Nguyen NK, Sukumar S. Clin Cancer Res. 2013 Apr 1;19(7):1651–9. PubMed Europe PMC Scholia
- PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20. PubMed Europe PMC Scholia
- AACR Project GENIE: Powering Precision Medicine through an International Consortium. AACR Project GENIE Consortium. Cancer Discov. 2017 Aug;7(8):818–31. PubMed Europe PMC Scholia