KEGG   PATHWAY: oaa05222
Entry
oaa05222                    Pathway                                
Name
Small cell lung cancer - Ornithorhynchus anatinus (platypus)
Description
Lung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% of all lung cancer cases. Molecular mechanisms altered in SCLC include induced expression of oncogene, MYC, and loss of tumorsuppressor genes, such as p53, PTEN, RB, and FHIT. The overexpression of MYC proteins in SCLC is largely a result of gene amplification. Such overexpression leads to more rapid proliferation and loss of terminal differentiation. Mutation or deletion of p53 or PTEN can lead to more rapid proliferation and reduced apoptosis. The retinoblastoma gene RB1 encodes a nuclear phosphoprotein that helps to regulate cell-cycle progression. The fragile histidine triad gene FHIT encodes the enzyme diadenosine triphosphate hydrolase, which is thought to have an indirect role in proapoptosis and cell-cycle control.
Class
Human Diseases; Cancer: specific types
Pathway map
oaa05222  Small cell lung cancer
oaa05222

Organism
Ornithorhynchus anatinus (platypus) [GN:oaa]
Gene
100074241  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
100075704  retinoic acid receptor beta isoform X1 [KO:K08528]
114813900  retinoic acid receptor beta-like [KO:K08528]
100074625  retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
114811257  retinoic acid receptor RXR-alpha-like [KO:K08524]
114817203  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
100092821  TP53; cellular tumor antigen p53 [KO:K04451]
114813305  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100081893  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
114814649  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
114813317  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
100088212  DDB2; DNA damage-binding protein 2 [KO:K10140]
100077423  POLK; DNA polymerase kappa isoform X2 [KO:K03511] [EC:2.7.7.7]
114807635  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100077443  cytochrome c [KO:K08738]
100073402  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
100092345  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
100087105  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100079391  MYC; myc proto-oncogene protein [KO:K04377]
100084460  MAX; protein max isoform X1 [KO:K04453]
100076280  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
114807863  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
100091822  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100075081  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100076085  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
103166602  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
100090228  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
114814505  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
100075784  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
100087197  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
100083537  RB1; retinoblastoma-associated protein [KO:K06618]
100087014  E2F1; transcription factor E2F1 [KO:K17454]
100085053  E2F2; transcription factor E2F2 [KO:K09389]
100090475  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
100084401  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
100073948  COL4A4; collagen alpha-4(IV) chain isoform X1 [KO:K06237]
100084415  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
100078067  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
100078102  COL4A6; collagen alpha-6(IV) chain [KO:K06237]
103170730  COL4A3; collagen alpha-3(IV) chain isoform X1 [KO:K06237]
100078011  LAMA2; LOW QUALITY PROTEIN: laminin subunit alpha-2 [KO:K05637]
100079917  LAMA1; laminin subunit alpha-1 [KO:K05637]
100074317  LAMA3; laminin subunit alpha-3 [KO:K06240]
100074506  LAMA5; laminin subunit alpha-5 [KO:K06240]
100074197  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
100078794  LAMB1; laminin subunit beta-1 [KO:K05636]
103170249  laminin subunit beta-2-like isoform X1 [KO:K06243]
100075055  LAMB2; laminin subunit beta-2 [KO:K06243]
100079022  LAMB3; laminin subunit beta-3 [KO:K06244]
100085738  LAMC1; LOW QUALITY PROTEIN: laminin subunit gamma-1 [KO:K05635]
100085748  LAMC2; laminin subunit gamma-2 [KO:K06246]
100075439  LAMC3; laminin subunit gamma-3 [KO:K06247]
100078116  FN1; fibronectin isoform X5 [KO:K05717]
100076348  ITGA2; integrin alpha-2 [KO:K06481]
114815046  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
100080433  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
100084141  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
100085661  ITGAV; integrin alpha-V [KO:K06487]
100073959  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
100076789  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
100086270  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100073788  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100074273  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100080187  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
100082075  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
103167126  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
100074365  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
100083320  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100081473  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100090267  AKT2; RAC-beta serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100082351  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
100078925  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100073613  IKBKG; NF-kappa-B essential modulator [KO:K07210]
100090081  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100083819  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100074633  RELA; transcription factor p65 isoform X1 [KO:K04735]
100077243  baculoviral IAP repeat-containing protein 2 [KO:K16060]
100079889  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100074804  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
107546921  BCL2L1; bcl-2-like protein 1 [KO:K04570]
100681677  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
100681935  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
100681066  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
100075919  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
100681634  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
100078367  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
100077058  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100086096  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
100075386  NOS2; nitric oxide synthase, inducible isoform X1 [KO:K13241] [EC:1.14.13.39]
Compound
C00777  Retinoate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C15493  9-cis-Retinoic acid
Reference
PMID:12379883
  Authors
Osada H, Takahashi T.
  Title
Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer.
  Journal
Oncogene 21:7421-34 (2002)
DOI:10.1038/sj.onc.1205802
Reference
PMID:12741677
  Authors
Yokota J, Nishioka M, Tani M, Kohno T.
  Title
Genetic alterations responsible for metastatic phenotypes of lung cancer cells.
  Journal
Clin Exp Metastasis 20:189-93 (2003)
DOI:10.1023/a:1022978932215
Reference
PMID:12711111
  Authors
Sanchez-Cespedes M.
  Title
Dissecting the genetic alterations involved in lung carcinogenesis.
  Journal
Lung Cancer 40:111-21 (2003)
DOI:10.1016/S0169-5002(03)00033-3
Reference
PMID:12407699
  Authors
Mitsuuchi Y, Testa JR.
  Title
Cytogenetics and molecular genetics of lung cancer.
  Journal
Am J Med Genet 115:183-8 (2002)
DOI:10.1002/ajmg.10692
Reference
PMID:11720739
  Authors
Kaye FJ.
  Title
Molecular biology of lung cancer.
  Journal
Lung Cancer 34 Suppl 2:S35-41 (2001)
DOI:10.1016/S0169-5002(01)00342-7
Reference
PMID:16112428
  Authors
Panani AD, Roussos C.
  Title
Cytogenetic and molecular aspects of lung cancer.
  Journal
Cancer Lett 239:1-9 (2006)
DOI:10.1016/j.canlet.2005.06.030
Reference
PMID:11902573
  Authors
Altucci L, Gronemeyer H.
  Title
The promise of retinoids to fight against cancer.
  Journal
Nat Rev Cancer 1:181-93 (2001)
DOI:10.1038/35106036
Reference
PMID:10944551
  Authors
Virmani AK, Rathi A, Zochbauer-Muller S, Sacchi N, Fukuyama Y, Bryant D, Maitra A, Heda S, Fong KM, Thunnissen F, Minna JD, Gazdar AF.
  Title
Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas.
  Journal
J Natl Cancer Inst 92:1303-7 (2000)
DOI:10.1093/jnci/92.16.1303
Reference
PMID:11807782
  Authors
Sartorius UA, Krammer PH.
  Title
Upregulation of Bcl-2 is involved in the mediation of chemotherapy resistance in human small cell lung cancer cell lines.
  Journal
Int J Cancer 97:584-92 (2002)
DOI:10.1002/ijc.10096
Reference
PMID:16064138
  Authors
Adhikary S, Eilers M.
  Title
Transcriptional regulation and transformation by Myc proteins.
  Journal
Nat Rev Mol Cell Biol 6:635-45 (2005)
DOI:10.1038/nrm1703
Reference
PMID:11463388
  Authors
Spruck C, Strohmaier H, Watson M, Smith AP, Ryan A, Krek TW, Reed SI.
  Title
A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1.
  Journal
Mol Cell 7:639-50 (2001)
DOI:10.1016/S1097-2765(01)00210-6
Reference
PMID:15109562
  Authors
Buttery RC, Rintoul RC, Sethi T.
  Title
Small cell lung cancer: the importance of the extracellular matrix.
  Journal
Int J Biochem Cell Biol 36:1154-60 (2004)
DOI:10.1016/S1357-2725(03)00261-9
Reference
PMID:11559746
  Authors
Yamada KM, Araki M.
  Title
Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis.
  Journal
J Cell Sci 114:2375-82 (2001)
Reference
PMID:11905738
  Authors
Rintoul RC, Sethi T.
  Title
The role of extracellular matrix in small-cell lung cancer.
  Journal
Lancet Oncol 2:437-42 (2001)
DOI:10.1016/S1470-2045(00)00421-6
Reference
PMID:12243753
  Authors
Ekedahl J, Joseph B, Grigoriev MY, Muller M, Magnusson C, Lewensohn R, Zhivotovsky B.
  Title
Expression of inhibitor of apoptosis proteins in small- and non-small-cell lung carcinoma cells.
  Journal
Exp Cell Res 279:277-90 (2002)
DOI:10.1006/excr.2002.5608
Reference
PMID:12616528
  Authors
Shivapurkar N, Reddy J, Chaudhary PM, Gazdar AF.
  Title
Apoptosis and lung cancer: a review.
  Journal
J Cell Biochem 88:885-98 (2003)
DOI:10.1002/jcb.10440
Reference
PMID:23070004
  Authors
Weyhenmeyer B, Murphy AC, Prehn JH, Murphy BM
  Title
Targeting the anti-apoptotic Bcl-2 family members for the treatment of cancer.
  Journal
Exp Oncol 34:192-9 (2012)
Related
pathway
oaa04110  Cell cycle
oaa04115  p53 signaling pathway
oaa04151  PI3K-Akt signaling pathway
oaa04210  Apoptosis
oaa04510  Focal adhesion
oaa04512  ECM-receptor interaction
KO pathway
ko05222   

  All links  
Genome (1)   
   KEGG GENOME (1)   
Gene (89)   
   KEGG GENES (89)   
All databases (90)   

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