KEGG   PATHWAY: dle05222
Entry
dle05222                    Pathway                                

Name
Small cell lung cancer - Delphinapterus leucas (beluga whale)
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
dle05222  Small cell lung cancer
dle05222

Organism
Delphinapterus leucas (beluga whale) [GN:dle]
Gene
111174232  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
111164795  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
111177070  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
111178670  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
111169246  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
111185755  TP53; cellular tumor antigen p53 [KO:K04451]
111178743  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
111170922  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
111178438  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
111167640  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
111180640  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
111178690  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
111183968  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
111185272  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
111180199  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
111180543  cytochrome c [KO:K08738]
111174575  cytochrome c-like [KO:K08738]
111174031  cytochrome c-like [KO:K08738]
111172911  cytochrome c 2 [KO:K08738]
111174197  cytochrome c-like [KO:K08738]
111175930  cytochrome c-like [KO:K08738]
111187821  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
111187099  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
111173401  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
111164391  MYC; myc proto-oncogene protein [KO:K04377]
111173064  MAX; protein max isoform X1 [KO:K04453]
111187191  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
111163122  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
111173824  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
111180943  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
111183632  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
111167048  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
111167654  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
111187525  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
111176781  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
111173897  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
111180416  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
111180958  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
111175081  RB1; retinoblastoma-associated protein [KO:K06618]
111184273  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
111163373  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
111181407  E2F3; transcription factor E2F3 isoform X2 [KO:K06620]
111171889  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
111171891  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
111165780  COL4A5; collagen alpha-5(IV) chain [KO:K06237]
111165781  COL4A6; collagen alpha-6(IV) chain [KO:K06237]
111176383  COL4A2; collagen alpha-2(IV) chain isoform X1 [KO:K06237]
111176384  COL4A1; collagen alpha-1(IV) chain isoform X1 [KO:K06237]
111163079  LAMA1; laminin subunit alpha-1 isoform X1 [KO:K05637]
111168261  LAMA2; laminin subunit alpha-2 [KO:K05637]
111181472  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
111186816  LAMA5; laminin subunit alpha-5 [KO:K06240]
111164771  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
111184472  LAMB1; laminin subunit beta-1 [KO:K05636]
111174406  LAMB2; laminin subunit beta-2 isoform X1 [KO:K06243]
111184724  LAMB3; laminin subunit beta-3 [KO:K06244]
111184566  LAMB4; LOW QUALITY PROTEIN: laminin subunit beta-4 [KO:K06245]
111184636  LAMC1; laminin subunit gamma-1 [KO:K05635]
111184637  LAMC2; laminin subunit gamma-2 [KO:K06246]
111177115  LAMC3; laminin subunit gamma-3 [KO:K06247]
111171803  FN1; fibronectin isoform X1 [KO:K05717]
111186789  ITGA2; integrin alpha-2 [KO:K06481]
111170236  ITGA2B; integrin alpha-IIb [KO:K06476]
111166388  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
111172869  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
111171639  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
111178037  ITGB1; integrin beta-1 [KO:K05719]
111165046  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
111173839  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111179235  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111187262  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
111166652  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111185984  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111175760  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
111172530  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]
111177559  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111176008  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111180855  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111172396  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
111173552  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
111170969  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
111173225  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
111179110  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
111183745  RELA; transcription factor p65 isoform X1 [KO:K04735]
111168369  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
111168370  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
111168228  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
111186670  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
111184326  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
111177267  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
111177009  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
111176049  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
111185690  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
111184706  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
111179772  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
111184673  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
111185989  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
dle04110  Cell cycle
dle04115  p53 signaling pathway
dle04151  PI3K-Akt signaling pathway
dle04210  Apoptosis
dle04510  Focal adhesion
dle04512  ECM-receptor interaction
KO pathway
ko05222   
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