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. f51 ea7 e17 ff3 d76 parentid=P06400; parentsymbol=RB1; site=AVIPINGsPRtPRRG; position=ser249; sitegrpid=447975; ptm=p; direction=d parentid=P31749; parentsymbol=AKT1; site=kDGAtMKtFCGtPEy; position=thr308; sitegrpid=447856; ptm=ub; direction=u parentid=Q92934; parentsymbol=BAD; site=KGLPRPKsAGtAtQM; position=ser134; sitegrpid=447864; ptm=p; direction=d parentid=Q92934; parentsymbol=BAD; site=PFrGrsRsAPPNLWA; position=ser99; sitegrpid=447862; ptm=p; direction=d parentid=P31749; parentsymbol=AKT1; site=RPHFPQFsysAsGtA; position=ser473; sitegrpid=447855; ptm=ub; direction=u parentid=Q02750; parentsymbol=MAP2K1; site=LIDsMANsFVGtRSY; position=ser222; sitegrpid=448513; ptm=p; direction=u parentid=Q02750; parentsymbol=MAP2K1; site=VsGQLIDsMANsFVG; position=ser218; sitegrpid=448514; ptm=p; direction=u parentid=P36507; parentsymbol=MAP2K2; site=LIDsMANsFVGtRSY; position=ser226; sitegrpid=448074; ptm=p; direction=u parentid=P36507; parentsymbol=MAP2K2; site=VsGQLIDsMANsFVG; position=ser222; sitegrpid=448073; ptm=p; direction=u parentid=P28482; parentsymbol=MAPK1; site=HtGFLtEyVAtRWyr; position=tyr187; sitegrpid=447594; ptm=p; direction=u parentid=P28482; parentsymbol=MAPK1; site=HDHtGFLtEyVAtRW; position=thr185; sitegrpid=447593; ptm=p; direction=u parentid=P27361; parentsymbol=MAPK3; site=HDHtGFLtEyVAtRW; position=thr202; sitegrpid=447542; ptm=p; direction=u parentid=P27361; parentsymbol=MAPK3; site=HtGFLtEyVAtRWyr; position=tyr204; sitegrpid=447543; ptm=p; direction=u parentid=P19174; parentsymbol=PLCG1; site=EGsFEsRyQQPFEDF; position=tyr1253; sitegrpid=448576; ptm=p; direction=u parentid=P19174; parentsymbol=PLCG1; site=EGRNPGFyVEANPMP; position=tyr783; sitegrpid=447667; ptm=p; direction=u parentid=P19174; parentsymbol=PLCG1; site=IGtAEPdyGALyEGR; position=tyr771; sitegrpid=448575; ptm=p; direction=u parentid=P31751; parentsymbol=AKT2; site=sDGAtMKtFCGtPEy; position=thr309; sitegrpid=448537; ptm=p; direction=u parentid=P55211; parentsymbol=CASP9; site=kLRRRFssLHFMVEV; position=ser196; sitegrpid=448454; ptm=p; direction=d parent=O43524; position=ser253; ptm=p; direction=d parent=O43524; position=thr32; ptm=p; direction=d parentid=P42229; parentsymbol=STAT5A; site=LAkAVDGyVkPQIkQ; position=tyr694; sitegrpid=447767; ptm=p; direction=u b72 d67 17328863 PubMed Induction of apoptosis by tumor suppressor FHIT via death receptor signaling pathway in human lung cancer cells. Biochem Biophys Res Commun 2007 Deng WG Nishizaki M Fang B Roth JA Ji L lung cancer pathway PW:0000703 Pathway Ontology 25514926 PubMed PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res 2015 Hornbeck PV Zhang B Murray B Kornhauser JM Latham V Skrzypek E 17328863 PubMed Induction of apoptosis by tumor suppressor FHIT via death receptor signaling pathway in human lung cancer cells. Biochem Biophys Res Commun 2007 Deng WG Nishizaki M Fang B Roth JA Ji L 28572459 PubMed AACR Project GENIE: Powering Precision Medicine through an International Consortium. Cancer Discov 2017 23322901 PubMed Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment. Clin Cancer Res 2013 Connolly RM Nguyen NK Sukumar S disease pathway PW:0000013 Pathway Ontology 20418096 PubMed The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer 2010 Sasaki T Rodig SJ Chirieac LR Jänne PA map05223 KEGG Pathway KEGG Non-small cell lung cancer https://www.kegg.jp/dbget-bin/www_bget?pathway+map05223 lung cancer DOID:1324 Disease cancer pathway PW:0000605 Pathway Ontology bronchial epithelial cell CL:0002328 Cell Type