Non-small cell lung cancer (Homo sapiens)

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ArcPathVisio Brace Ellipse EndoplasmicReticulum GolgiApparatus HexagonPathVisio MimDegradation Mitochondria Octagon PentagonPathVisio Rectangle RoundedRectangle SarcoplasmicReticulum TriangleEquilateralEast TrianglePathVisio none ERProliferationActivating mutationDNA damageLegendAnti-apoptosisEGFDAGTGFAPIP3KRASPDK1OmacetaxinemepesuccinatePRB1Ca2+CDKN2ARASSF1JAK3Retinoic acidIP3STK4CalciumsignalingTP53PIK3CAPIK3CBPIK3CDPRKCAPRKCBPRKCGHRASKRASNRASBAK1CDKN1ABAXDDB2GADD45AGADD45BGADD45GPOLKPIK3R1PIK3CAPIK3CBPIK3CDPIK3R2PIK3R3EGFRERBB2BinimetinibTrametinibPimasertibSelumetinibCobimetinibCDK4CDK6CCND1PPAKT1PAKT2AKT3PPBADPCASP9PPFOXO3CRABP1CRABP2EML4ALKRARBRXRARXRBRXRGGRB2SOS1SOS2ARAFBRAFRAF1PPMAP2K1PPMAP2K2PPMAPK1PPMAPK3PPPPLCG1PLCG2PI3K-Akt signalingSTAT3PSTAT5ASTAT5BCell survivalRas signalingCCND1RASSF5Reduced apoptosisE2F1E2F2E2F3G1 to S progressionp53 signalingCell cycleCell cycleInactivating mutationCASP8FHITBIDReduced apoptosisCell-cycle progressionCASP3CASP9CYCSRetinoic acidUncontrolled proliferationIncreased survivalGenomic instabilityTumor progressionName: Non-small cell lung cancerOrganism: Homo sapiens


Description

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 [KEGG](https://www.kegg.jp/dbget-bin/www_bget?pathway+map05223). Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.

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Quality Tags

Image:Curated.pngApproved version
Image:Wplogo_31.pngCommunity: CPTAC
Image:MissingXref.pngAnnotate nodes

Ontology Terms

 

Bibliography

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  1. Deng WG, Nishizaki M, Fang B, Roth JA, Ji L; ''Induction of apoptosis by tumor suppressor FHIT via death receptor signaling pathway in human lung cancer cells.''; Biochem Biophys Res Commun, 2007 PubMed Europe PMC Scholia
  2. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E; ''PhosphoSitePlus, 2014: mutations, PTMs and recalibrations.''; Nucleic Acids Res, 2015 PubMed Europe PMC Scholia
  3. Sasaki T, Rodig SJ, Chirieac LR, Jänne PA; ''The biology and treatment of EML4-ALK non-small cell lung cancer.''; Eur J Cancer, 2010 PubMed Europe PMC Scholia
  4. ''KEGG Non-small cell lung cancer''; https://www.kegg.jp/dbget-bin/www_bget?pathway+map05223,
  5. ''AACR Project GENIE: Powering Precision Medicine through an International Consortium.''; Cancer Discov, 2017 PubMed Europe PMC Scholia
  6. Connolly RM, Nguyen NK, Sukumar S; ''Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment.''; Clin Cancer Res, 2013 PubMed Europe PMC Scholia
  7. Deng WG, Nishizaki M, Fang B, Roth JA, Ji L; ''Induction of apoptosis by tumor suppressor FHIT via death receptor signaling pathway in human lung cancer cells.''; Biochem Biophys Res Commun, 2007 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
138079view22:42, 13 March 2025EweitzRefine state position
138069view12:43, 13 March 2025EweitzOntology Term : 'lung large cell carcinoma' added !
138068view12:42, 13 March 2025EweitzOntology Term : 'lung adenocarcinoma' added !
138067view12:42, 13 March 2025EweitzOntology Term : 'squamous cell carcinoma' added !
138066view12:41, 13 March 2025EweitzModified description
138064view12:29, 13 March 2025EweitzOntology Term : 'lung non-small cell carcinoma' added !
138060view12:23, 13 March 2025EweitzMitigate PathVisio / Kaavio graphical discrepancy
138059view12:20, 13 March 2025EweitzFix PathVisio / Kaavio graphical discrepancy
138058view12:20, 13 March 2025EweitzStandardize case
138057view12:18, 13 March 2025EweitzRefine state position
138056view12:10, 13 March 2025EweitzEconomize layout
138055view12:07, 13 March 2025EweitzStandardize case
138054view12:05, 13 March 2025EweitzEconomize layout
138053view12:02, 13 March 2025EweitzEconomize layout
138052view11:54, 13 March 2025EweitzEconomize layout
138051view11:47, 13 March 2025EweitzEconomize layout
138049view11:45, 13 March 2025EweitzStack nodes
138048view11:40, 13 March 2025EweitzTailor node height
137089view22:06, 27 February 2025KhanspersModified description
127755view18:51, 2 December 2023EgonwChEBI id for Ca2+ instead of the "Ca" atom
127573view17:25, 23 October 2023KhanspersModified description
127490view17:13, 11 October 2023Khanspersupdated phosphosites
127237view20:18, 25 August 2023Khanspersadded lit ref and updated description
123348view10:42, 17 July 2022EgonwMade five pathways clickable
119279view10:42, 23 June 2021Finterlyadded KEGG pathway info to publicationXref
108128view10:28, 29 November 2019FehrhartOntology Term : 'lung cancer' added !
108127view10:28, 29 November 2019FehrhartOntology Term : 'cancer pathway' added !
105677view22:54, 12 August 2019Khanspersadded drugs
105676view22:28, 12 August 2019Khanspersupdated outcomes
105481view05:38, 8 August 2019KhanspersModified description
105444view04:55, 8 August 2019KhanspersModified description
105192view23:10, 17 July 2019KhanspersModified description
105191view23:09, 17 July 2019Khanspersupdated lit refs
105190view22:42, 17 July 2019Khanspersupdated ERBB2
105189view22:33, 17 July 2019Khanspersadded lit ref
105155view23:21, 12 July 2019Khanspersadded details for retinoic acid signaling and added new interaction type
105154view22:21, 12 July 2019Khanspersupdate FHIT section
105004view04:55, 28 June 2019KhanspersModified description
96916view14:37, 19 April 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
96911view04:38, 19 April 2018Khanspersupdated kras
96909view19:34, 18 April 2018Khanspersadded pathway node xrefs
96857view23:28, 14 April 2018AlexanderPicoOntology Term : 'disease pathway' added !
96856view00:06, 14 April 2018KhanspersOntology Term : 'bronchial epithelial cell' added !
96855view00:05, 14 April 2018KhanspersOntology Term : 'lung cancer pathway' added !
96854view00:05, 14 April 2018KhanspersModified description
96853view00:03, 14 April 2018KhanspersModified description
96852view23:58, 13 April 2018KhanspersNew pathway

External references

DataNodes

View all...
Name  ↓Type  ↓Database reference  ↓Comment  ↓
AKT1GeneProductENSG00000142208 (Ensembl)
AKT2GeneProductENSG00000105221 (Ensembl)
AKT3GeneProductENSG00000117020 (Ensembl)
ALKGeneProductENSG00000171094 (Ensembl)
ARAFGeneProductENSG00000078061 (Ensembl)
BADGeneProductENSG00000002330 (Ensembl)
BAK1GeneProductENSG00000030110 (Ensembl)
BAXGeneProductENSG00000087088 (Ensembl)
BIDGeneProductENSG00000015475 (Ensembl)
BRAFGeneProductENSG00000157764 (Ensembl)
BinimetinibMetaboliteQ19903515 (Wikidata)
CASP3GeneProductENSG00000164305 (Ensembl)
CASP8GeneProductENSG00000064012 (Ensembl)
CASP9GeneProductENSG00000132906 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl)
CDK4GeneProductENSG00000135446 (Ensembl)
CDK6GeneProductENSG00000105810 (Ensembl)
CDKN1AGeneProductENSG00000124762 (Ensembl)
CDKN2AGeneProductENSG00000147889 (Ensembl)
CRABP1GeneProductENSG00000166426 (Ensembl)
CRABP2GeneProductENSG00000143320 (Ensembl)
CYCSGeneProductENSG00000172115 (Ensembl)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Calcium signalingPathway
Cell cyclePathwayWP179 (WikiPathways)
CobimetinibMetaboliteQ15708292 (Wikidata)
DAGMetaboliteCHEBI:18035 (ChEBI)
DDB2GeneProductENSG00000134574 (Ensembl)
E2F1GeneProductENSG00000101412 (Ensembl)
E2F2GeneProductENSG00000007968 (Ensembl)
E2F3GeneProductENSG00000112242 (Ensembl)
EGFGeneProductENSG00000138798 (Ensembl)
EGFRGeneProductENSG00000146648 (Ensembl)
EML4GeneProductENSG00000143924 (Ensembl)
ERBB2GeneProductENSG00000141736 (Ensembl)
FHITGeneProductENSG00000189283 (Ensembl)
FOXO3GeneProductENSG00000118689 (Ensembl)
GADD45AGeneProductENSG00000116717 (Ensembl)
GADD45BGeneProductENSG00000099860 (Ensembl)
GADD45GGeneProductENSG00000130222 (Ensembl)
GRB2GeneProductGRB2 (HGNC)
HRASGeneProductENSG00000174775 (Ensembl)
IP3MetaboliteCHEBI:16595 (ChEBI)
JAK3GeneProductENSG00000105639 (Ensembl)
KRASGeneProductENSG00000133703 (Ensembl)
MAP2K1GeneProductENSG00000169032 (Ensembl)
MAP2K2GeneProductENSG00000126934 (Ensembl)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
NRASGeneProductENSG00000213281 (Ensembl)
Omacetaxine mepesuccinateMetaboliteCHEBI:71019 (ChEBI)
PDK1GeneProductENSG00000152256 (Ensembl)
PI3K-Akt signalingPathwayWP4172 (WikiPathways)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CBGeneProductENSG00000051382 (Ensembl)
PIK3CDGeneProductENSG00000171608 (Ensembl)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PIK3R2GeneProductENSG00000105647 (Ensembl)
PIK3R3GeneProductENSG00000117461 (Ensembl)
PIP3MetaboliteCHEBI:16618 (ChEBI)
PLCG1GeneProductENSG00000124181 (Ensembl)
PLCG2GeneProductENSG00000197943 (Ensembl)
POLKGeneProductENSG00000122008 (Ensembl)
PRKCAGeneProductENSG00000154229 (Ensembl)
PRKCBGeneProductENSG00000166501 (Ensembl)
PRKCGGeneProductENSG00000126583 (Ensembl)
PimasertibMetaboliteQ27088393 (Wikidata)
RAF1GeneProductENSG00000132155 (Ensembl)
RARBGeneProductENSG00000077092 (Ensembl)
RASSF1GeneProductENSG00000068028 (Ensembl)
RASSF5GeneProductENSG00000266094 (Ensembl)
RB1GeneProductENSG00000139687 (Ensembl)
RXRAGeneProductENSG00000186350 (Ensembl)
RXRBGeneProductENSG00000204231 (Ensembl)
RXRGGeneProductENSG00000143171 (Ensembl)
Ras signalingPathwayWP4223 (WikiPathways)
Retinoic acidMetaboliteCHEBI:6067 (ChEBI)
SOS1GeneProductENSG00000115904 (Ensembl)
SOS2GeneProductENSG00000100485 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl)
STAT5AGeneProductENSG00000126561 (Ensembl)
STAT5BGeneProductENSG00000173757 (Ensembl)
STK4GeneProductENSG00000101109 (Ensembl)
SelumetinibMetaboliteCHEBI:90227 (ChEBI)
TGFAGeneProductENSG00000163235 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
TrametinibMetaboliteQ7833138 (Wikidata)
p53 signalingPathwayWP707 (WikiPathways)

Annotated Interactions

No annotated interactions

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