Non-small cell lung cancer (WP4255)
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. Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.
AuthorsKristina Hanspers , Alex Pico , Egon Willighagen , Friederike Ehrhart , and Finterly Hu
Discuss this pathway
- 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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OrganismsHomo sapiens CPTAC Diseases
Disease Ontologylung cancer
Pathway Ontologycancer pathway lung cancer pathway disease pathway
Cell Type Ontologybronchial epithelial cell
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