KEGG   PATHWAY: pteh05222
Entry
pteh05222                   Pathway                                
Name
Small cell lung cancer - Piliocolobus tephrosceles (Ugandan red Colobus)
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
pteh05222  Small cell lung cancer
pteh05222

Organism
Piliocolobus tephrosceles (Ugandan red Colobus) [GN:pteh]
Gene
111533955  FHIT; bis(5'-adenosyl)-triphosphatase isoform X2 [KO:K01522] [EC:3.6.1.29]
111539463  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
111523996  photoreceptor-specific nuclear receptor-like [KO:K08524]
111534772  retinoic acid receptor RXR-alpha [KO:K08524]
111542907  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
111539204  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
111527100  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
111542983  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
111541101  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
111528537  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
111520681  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
111520083  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
111542928  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
111544893  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
111539938  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
111528437  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
111528103  cytochrome c-like [KO:K08738]
111541425  cytochrome c [KO:K08738]
111551227  cytochrome c-like [KO:K08738]
111551298  cytochrome c-like [KO:K08738]
111551797  cytochrome c [KO:K08738]
111551867  cytochrome c [KO:K08738]
111543337  cytochrome c-like [KO:K08738]
111543628  cytochrome c-like [KO:K08738]
111534452  cytochrome c-like [KO:K08738]
111545049  cytochrome c-like [KO:K08738]
111555014  cytochrome c-like [KO:K08738]
111524229  cytochrome c [KO:K08738]
111525268  cytochrome c-like [KO:K08738]
111539464  cytochrome c-like [KO:K08738]
111526887  cytochrome c-like [KO:K08738]
111540111  cytochrome c-like [KO:K08738]
111520510  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
111527287  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
111551382  caspase-3-like isoform X1 [KO:K02187] [EC:3.4.22.56]
111548479  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
111550563  MYC; myc proto-oncogene protein [KO:K04377]
111555948  MAX; protein max isoform X1 [KO:K04453]
111527291  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
111537212  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
111541790  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
111552475  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
111522272  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
111543735  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
111527969  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
111545519  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
111552085  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
111541872  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
111553938  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
111549709  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
111523077  RB1; retinoblastoma-associated protein [KO:K06618]
111548151  E2F1; transcription factor E2F1 [KO:K17454]
111547703  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
111541114  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
111536673  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
111546314  COL4A1; collagen alpha-1(IV) chain isoform X1 [KO:K06237]
111546316  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
111527511  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
111527529  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
111536655  collagen alpha-6(IV) chain-like [KO:K06237]
111554928  LAMA2; laminin subunit alpha-2 [KO:K05637]
111553579  LAMA1; laminin subunit alpha-1 [KO:K05637]
111520480  laminin subunit alpha-5 [KO:K06240]
111539764  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
111547317  LAMA4; laminin subunit alpha-4 [KO:K06241]
111520373  LAMB1; laminin subunit beta-1 [KO:K05636]
111555391  LAMB2; laminin subunit beta-2 [KO:K06243]
111531101  LAMB3; laminin subunit beta-3 [KO:K06244]
111520401  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
111536950  LAMC1; laminin subunit gamma-1 [KO:K05635]
111536949  LAMC2; laminin subunit gamma-2 [KO:K06246]
111545964  LAMC3; laminin subunit gamma-3 [KO:K06247]
111548154  FN1; fibronectin isoform X1 [KO:K05717]
111541653  ITGA2; integrin alpha-2 isoform X1 [KO:K06481]
111525821  ITGA2B; integrin alpha-IIb [KO:K06476]
111537562  ITGA3; integrin alpha-3 [KO:K06482]
111522158  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
111542813  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
111546659  ITGB1; integrin beta-1 [KO:K05719]
111553372  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
111521403  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111544647  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111523340  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
111554247  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111539891  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111548774  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
111551321  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
111554120  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111545216  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111538340  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111538794  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
111544093  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
111524454  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
111547971  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
111522422  RELA; transcription factor p65 isoform X1 [KO:K04735]
111540065  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
111540066  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
111532918  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
111520493  BIRC7; baculoviral IAP repeat-containing protein 7 isoform X1 [KO:K16061]
111548123  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
111550331  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
111553030  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
111538162  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
111520789  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
111531090  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
111521878  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
111536921  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
111520811  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
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
pteh04110  Cell cycle
pteh04115  p53 signaling pathway
pteh04151  PI3K-Akt signaling pathway
pteh04210  Apoptosis
pteh04510  Focal adhesion
pteh04512  ECM-receptor interaction
KO pathway
ko05222   
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