KEGG   PATHWAY: ecb05222
Entry
ecb05222                    Pathway                                

Name
Small cell lung cancer - Equus caballus (horse)
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
ecb05222  Small cell lung cancer
ecb05222

Organism
Equus caballus (horse) [GN:ecb]
Gene
100057165  FHIT; bis(5'-adenosyl)-triphosphatase isoform X2 [KO:K01522] [EC:3.6.1.29]
100051546  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
100069096  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
100061303  RXRB; retinoic acid receptor RXR-beta isoform X3 [KO:K08525]
100060371  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
100062044  TP53; cellular tumor antigen p53 [KO:K04451]
100064022  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100054996  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100059768  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100630299  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100054674  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
100061755  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
100051180  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
100065534  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
100050934  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
100053958  CYCS; cytochrome c [KO:K08738]
111768755  cytochrome c, testis-specific [KO:K08738]
100052552  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
100054331  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
100034083  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100068097  MYC; myc proto-oncogene protein [KO:K04377]
100062536  MAX; protein max isoform X2 [KO:K04453]
100050436  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X2 [KO:K10500]
100034122  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100051005  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
100061625  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
102149114  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100630884  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
106782489  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
100053697  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
111773925  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100051790  CDK2; cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
100055302  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
100053882  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
100057080  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
100069192  E2F1; transcription factor E2F1 [KO:K17454]
100057866  E2F2; transcription factor E2F2 isoform X2 [KO:K09389]
100052248  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
100062160  COL4A4; collagen alpha-4(IV) chain isoform X1 [KO:K06237]
100066148  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
100060112  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
100054545  COL4A5; collagen alpha-5(IV) chain isoform X5 [KO:K06237]
100066264  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
100037402  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
100059860  LAMA1; laminin subunit alpha-1 isoform X1 [KO:K05637]
100073067  LAMA2; laminin subunit alpha-2 isoform X3 [KO:K05637]
791238  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
100058057  LAMA5; laminin subunit alpha-5 [KO:K06240]
100066875  LAMA4; laminin subunit alpha-4 isoform X2 [KO:K06241]
100060360  LAMB1; laminin subunit beta-1 [KO:K05636]
100053539  LAMB2; laminin subunit beta-2 isoform X1 [KO:K06243]
100056564  LAMB3; laminin subunit beta-3 [KO:K06244]
100060434  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
100055269  LAMC1; laminin subunit gamma-1 [KO:K05635]
791245  LAMC2; laminin subunit gamma-2 precursor [KO:K06246]
100069663  LAMC3; laminin subunit gamma-3 [KO:K06247]
100034189  FN1; fibronectin isoform X1 [KO:K05717]
100063367  ITGA2; integrin alpha-2 [KO:K06481]
100009697  ITGA2B; integrin alpha-IIb precursor [KO:K06476]
100056202  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
100064056  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
100068706  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
100055024  ITGB1; integrin beta-1 precursor [KO:K05719]
100058245  PTK2; focal adhesion kinase 1 isoform X12 [KO:K05725] [EC:2.7.10.2]
100051623  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100058141  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100051753  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100052122  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100050227  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
100146348  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100062388  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]
100064671  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100054961  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100061130  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100070393  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100050167  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
100058432  IKBKG; NF-kappa-B essential modulator [KO:K07210]
100058000  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100067894  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X4 [KO:K02580]
100057483  RELA; transcription factor p65 [KO:K04735]
100061273  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
100068894  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
100060870  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
100147373  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
100053597  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
100067681  TRAF1; TNF receptor-associated factor 1 isoform X2 [KO:K03172]
100068006  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
100055110  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
100072085  TRAF4; TNF receptor-associated factor 4 isoform X1 [KO:K09848]
100055119  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
100052296  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
791253  PTGS2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:1.14.99.1]
791246  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
ecb04110  Cell cycle
ecb04115  p53 signaling pathway
ecb04151  PI3K-Akt signaling pathway
ecb04210  Apoptosis
ecb04510  Focal adhesion
ecb04512  ECM-receptor interaction
KO pathway
ko05222   
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