KEGG   PATHWAY: gvr05222
Entry
gvr05222                    Pathway                                
Name
Small cell lung cancer - Galeopterus variegatus (Sunda flying lemur)
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
gvr05222  Small cell lung cancer
gvr05222

Disease
H00013  Small cell lung cancer
Organism
Galeopterus variegatus (Sunda flying lemur) [GN:gvr]
Gene
103581851  [KO:K10500]
103584940  LAMB2; laminin subunit beta-2 [KO:K06243]
103585463  PIK3R3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103586159  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
103586162  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
103586173  LAMB4; laminin subunit beta-4 [KO:K06245]
103586174  LAMB1; laminin subunit beta-1 isoform X1 [KO:K05636]
103586572  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103586645  LAMC2; laminin subunit gamma-2 [KO:K06246]
103586651  LAMC1; laminin subunit gamma-1 [KO:K05635]
103586784  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103586861  E2F1; transcription factor E2F1 [KO:K17454]
103587023  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
103587254  LAMA2; laminin subunit alpha-2 [KO:K05637]
103587301  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
103587762  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
103587820  MYC; myc proto-oncogene protein [KO:K04377]
103587883  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103588373  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
103588377  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
103588765  LAMA5; LOW QUALITY PROTEIN: laminin subunit alpha-5 [KO:K06240]
103588798  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
103589266  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103589530  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
103589765  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
103590136  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103590229  [KO:K08738]
103590253  E2F3; transcription factor E2F3 [KO:K06620]
103590279  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103590490  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
103590595  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
103590624  E2F2; transcription factor E2F2 [KO:K09389]
103591124  ITGA2; integrin alpha-2 [KO:K06481]
103591400  TP53; cellular tumor antigen p53 [KO:K04451]
103591436  NFKBIA; LOW QUALITY PROTEIN: NF-kappa-B inhibitor alpha [KO:K04734]
103591675  RXRA; retinoic acid receptor RXR-alpha [KO:K08524]
103591725  [KO:K05636]
103592005  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
103592096  DDB2; DNA damage-binding protein 2 [KO:K10140]
103592695  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
103592767  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
103592918  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]
103593625  LAMA3; laminin subunit alpha-3 [KO:K06240]
103593663  RB1; retinoblastoma-associated protein [KO:K06618]
103593683  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103594063  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
103594181  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
103595334  RELA; transcription factor p65 [KO:K04735]
103595436  FN1; fibronectin [KO:K05717]
103596078  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
103596079  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
103596384  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103596636  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
103596970  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
103597016  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
103597025  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
103597559  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
103597936  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
103598268  LAMB3; laminin subunit beta-3 [KO:K06244]
103598325  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103598440  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
103598508  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
103598599  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
103598878  MAX; protein max isoform X1 [KO:K04453]
103599113  LAMC3; laminin subunit gamma-3 [KO:K06247]
103599657  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
103599731  LAMA4; laminin subunit alpha-4 [KO:K06241]
103599851  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
103600955  [KO:K06485]
103601167  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
103601646  ITGB1; integrin beta-1 [KO:K05719]
103602907  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
103603724  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
103604259  [KO:K10500]
103604367  IKBKG; NF-kappa-B essential modulator [KO:K07210]
103604568  NOS2; LOW QUALITY PROTEIN: nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
103604851  ITGAV; integrin alpha-V [KO:K06487]
103605497  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
103605698  [KO:K04456] [EC:2.7.11.1]
103605977  LAMA1; LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637]
103606240  ITGA2B; integrin alpha-IIb [KO:K06476]
103606686  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
103606818  [KO:K06487]
103607082  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103607313  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
103607349  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
103607716  [KO:K06237]
103608053  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
103608190  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
103608454  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103608705  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
103609174  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103609553  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
103610047  [KO:K03173] [EC:2.3.2.27]
103610678  [KO:K08738]
103610749  [KO:K04725] [EC:2.3.2.27]
103610793  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
103610988  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
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
gvr04110  Cell cycle
gvr04115  p53 signaling pathway
gvr04151  PI3K-Akt signaling pathway
gvr04210  Apoptosis
gvr04510  Focal adhesion
gvr04512  ECM-receptor interaction
KO pathway
ko05222   

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