KEGG   PATHWAY: pon05222
Entry
pon05222                    Pathway                                

Name
Small cell lung cancer - Pongo abelii (Sumatran orangutan)
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
pon05222  Small cell lung cancer
pon05222

Organism
Pongo abelii (Sumatran orangutan) [GN:pon]
Gene
100460961  FHIT; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
100439439  RARB; retinoic acid receptor beta isoform X3 [KO:K08528]
100460920  RXRB; retinoic acid receptor RXR-beta isoform X2 [KO:K08525]
100171682  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
100435218  TP53; cellular tumor antigen p53 [KO:K04451]
100453682  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100436665  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100452809  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100456437  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100450682  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
100460189  bcl-2 homologous antagonist/killer [KO:K14021]
100432001  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
100454099  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
100443121  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
100938429  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
100171479  CYCS; cytochrome c [KO:K08738]
100462404  cytochrome c-like [KO:K08738]
112128551  cytochrome c-like [KO:K08738]
100445149  cytochrome c-like [KO:K08738]
112128607  cytochrome c-like [KO:K08738]
112130824  cytochrome c-like [KO:K08738]
112132396  LOW QUALITY PROTEIN: cytochrome c 2-like [KO:K08738]
112133797  cytochrome c-like [KO:K08738]
112134675  cytochrome c-like [KO:K08738]
112134685  cytochrome c-like [KO:K08738]
112134371  cytochrome c-like [KO:K08738]
112134960  cytochrome c-like [KO:K08738]
112135506  cytochrome c-like [KO:K08738]
100459074  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
100460459  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
100435491  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100456735  MYC; myc proto-oncogene protein [KO:K04377]
100436950  MAX; protein max isoform X4 [KO:K04453]
100454123  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
100459175  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100443314  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
100454924  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100171625  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100454367  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
100462374  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
100432371  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
100449905  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100446748  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
100438282  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
100461587  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
100462155  RB1; retinoblastoma-associated protein [KO:K06618]
100435851  E2F1; transcription factor E2F1 [KO:K17454]
100458002  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
100448297  E2F3; transcription factor E2F3 isoform X3 [KO:K06620]
100457450  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
100457807  COL4A5; collagen alpha-5(IV) chain isoform X3 [KO:K06237]
100444160  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
100444523  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
100443710  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
100444077  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
100438698  LAMA1; laminin subunit alpha-1 [KO:K05637]
100458901  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
100439539  LAMA3; laminin subunit alpha-3 [KO:K06240]
100456580  LOW QUALITY PROTEIN: laminin subunit alpha-5-like [KO:K06240]
100458670  LAMB1; laminin subunit beta-1 [KO:K05636]
100441641  LAMB2; laminin subunit beta-2 isoform X1 [KO:K06243]
100434204  LAMB3; laminin subunit beta-3 [KO:K06244]
100461994  LAMB4; LOW QUALITY PROTEIN: laminin subunit beta-4 [KO:K06245]
100446999  LAMC1; laminin subunit gamma-1 [KO:K05635]
100446634  LAMC2; laminin subunit gamma-2 [KO:K06246]
100441462  LAMC3; laminin subunit gamma-3 [KO:K06247]
100449704  FN1; fibronectin isoform X1 [KO:K05717]
100452800  ITGA2B; integrin alpha-IIb [KO:K06476]
100459915  ITGA3; integrin alpha-3 [KO:K06482]
100442478  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
100451792  ITGAV; integrin alpha-V [KO:K06487]
100172223  ITGB1; integrin beta-1 precursor [KO:K05719]
100447959  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
100432846  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100453779  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103889133  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100174298  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100173589  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
100437617  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100171828  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]
100454279  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100448114  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100442100  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100174735  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
100440586  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X3 [KO:K07209] [EC:2.7.11.10]
100449496  IKBKG; NF-kappa-B essential modulator isoform X5 [KO:K07210]
100459445  NF-kappa-B inhibitor alpha [KO:K04734]
100461595  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100456049  RELA; transcription factor p65 [KO:K04735]
100457858  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
100457249  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
100449741  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
100432733  BIRC7; baculoviral IAP repeat-containing protein 7 isoform X2 [KO:K16061]
100937717  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase XIAP [KO:K16061]
100453051  BCL2L1; bcl-2-like protein 1 [KO:K04570]
100172676  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
100458089  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
100460079  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
100431446  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
100453867  TRAF5; TNF receptor-associated factor 5 isoform X2 [KO:K09849]
100449432  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100436566  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
100436584  NOS2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
Compound
C00777  Retinoate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C15493  9-cis-Retinoic acid
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
pon04110  Cell cycle
pon04115  p53 signaling pathway
pon04151  PI3K-Akt signaling pathway
pon04210  Apoptosis
pon04510  Focal adhesion
pon04512  ECM-receptor interaction
KO pathway
ko05222   
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