KEGG   PATHWAY: dro05222
Entry
dro05222                    Pathway                                

Name
Small cell lung cancer - Desmodus rotundus (common vampire bat)
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
dro05222  Small cell lung cancer
dro05222

Organism
Desmodus rotundus (common vampire bat) [GN:dro]
Gene
112301080  FHIT; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
112309976  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
112306469  RXRA; retinoic acid receptor RXR-alpha [KO:K08524]
112302171  RXRB; retinoic acid receptor RXR-beta [KO:K08525]
112322188  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
112308825  TP53; cellular tumor antigen p53 [KO:K04451]
112302262  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
112312410  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
112307265  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
112312272  growth arrest and DNA damage-inducible protein GADD45 beta-like [KO:K04402]
112309280  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
112310132  BAX; apoptosis regulator BAX [KO:K02159]
112302219  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
112303349  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
112307522  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
112322759  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
112306993  cytochrome c [KO:K08738]
112320658  cytochrome c-like [KO:K08738]
112322221  cytochrome c-like [KO:K08738]
112321814  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
112299456  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
112306749  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
112315592  MYC; myc proto-oncogene protein [KO:K04377]
112311197  MAX; protein max isoform X1 [KO:K04453]
112299134  ZBTB17; LOW QUALITY PROTEIN: zinc finger and BTB domain-containing protein 17 [KO:K10500]
112302879  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
112319119  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
112319896  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
112317273  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
112314333  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
112307279  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
112321074  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
112318485  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
112319068  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
112296785  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
112315543  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
112313044  RB1; retinoblastoma-associated protein [KO:K06618]
112303722  E2F1; transcription factor E2F1 [KO:K17454]
112298997  E2F2; transcription factor E2F2 [KO:K09389]
112309256  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
112321420  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
112321451  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
112296845  COL4A5; collagen alpha-5(IV) chain [KO:K06237]
112296867  COL4A6; LOW QUALITY PROTEIN: collagen alpha-6(IV) chain [KO:K06237]
112307731  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
112307910  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
112322610  LAMA1; laminin subunit alpha-1 [KO:K05637]
112297058  LAMA2; laminin subunit alpha-2 [KO:K05637]
112322675  laminin subunit alpha-3-like [KO:K06240]
112303887  LAMA5; laminin subunit alpha-5 [KO:K06240]
112302957  LAMB1; laminin subunit beta-1 [KO:K05636]
112309635  LAMB2; laminin subunit beta-2 [KO:K06243]
112309774  LOW QUALITY PROTEIN: laminin subunit beta-2-like [KO:K06243]
112297463  LAMB3; laminin subunit beta-3 [KO:K06244]
112302299  LAMB4; laminin subunit beta-4 [KO:K06245]
112297926  LAMC1; laminin subunit gamma-1 [KO:K05635]
112296770  LAMC2; laminin subunit gamma-2 [KO:K06246]
112306548  LAMC3; laminin subunit gamma-3 [KO:K06247]
112307828  FN1; fibronectin isoform X1 [KO:K05717]
112315265  ITGA2; integrin alpha-2 [KO:K06481]
112298771  ITGA2B; integrin alpha-IIb [KO:K06476]
112316285  ITGA3; integrin alpha-3 [KO:K06482]
112305805  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
112305765  ITGAV; integrin alpha-V [KO:K06487]
112317701  ITGB1; integrin beta-1 [KO:K05719]
112310002  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
112299448  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
112307667  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112321016  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112305224  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
112314466  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
112307354  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]
112311458  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112318919  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112320130  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112300474  CHUK; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
112321547  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
112296261  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
112296519  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
112317867  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
112317202  RELA; transcription factor p65 [KO:K04735]
112317544  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
112317519  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
112310530  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
112303893  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
112304196  BCL2L1; bcl-2-like protein 1 [KO:K04570]
112306476  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
112306448  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
112311693  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
112308504  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
112296542  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
112303407  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
112296707  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
112308600  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
dro04110  Cell cycle
dro04115  p53 signaling pathway
dro04151  PI3K-Akt signaling pathway
dro04210  Apoptosis
dro04510  Focal adhesion
dro04512  ECM-receptor interaction
KO pathway
ko05222   
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