KEGG   PATHWAY: pvp05222
Entry
pvp05222                    Pathway                                
Name
Small cell lung cancer - Pteropus vampyrus (large flying fox)
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
pvp05222  Small cell lung cancer
pvp05222

Disease
H00013  Small cell lung cancer
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288270  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
105288383  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105289673  ITGAV; LOW QUALITY PROTEIN: integrin alpha-V [KO:K06487]
105290030  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
105290063  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
105290414  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
105290449  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
105290842  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
105290979  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
105291123  FN1; fibronectin [KO:K05717]
105291179  LAMA2; laminin subunit alpha-2 [KO:K05637]
105291226  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
105291906  TRAF4; TNF receptor-associated factor 4 isoform X1 [KO:K09848]
105291934  NOS2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
105292271  LAMA3; laminin subunit alpha-3 isoform X2 [KO:K06240]
105292561  MYC; myc proto-oncogene protein [KO:K04377]
105292663  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
105292717  BCL2; apoptosis regulator Bcl-2 isoform X2 [KO:K02161]
105292827  LAMC1; laminin subunit gamma-1 isoform X1 [KO:K05635]
105292869  LAMC2; laminin subunit gamma-2 [KO:K06246]
105293029  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105293112  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X2 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
105293163  [KO:K08738]
105293923  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105294340  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
105294412  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
105294446  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
105294710  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
105294764  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
105294766  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
105295002  TRAF5; TNF receptor-associated factor 5 isoform X2 [KO:K09849]
105295029  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
105295219  LAMA4; laminin subunit alpha-4 [KO:K06241]
105295411  ITGA3; integrin alpha-3 isoform X2 [KO:K06482]
105295887  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
105296119  [KO:K06237]
105296151  COL4A6; collagen alpha-6(IV) chain [KO:K06237]
105296207  LAMA1; LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637]
105296378  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105297140  [KO:K02649]
105297999  RELA; transcription factor p65 [KO:K04735]
105298277  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
105298278  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
105298440  CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X4 [KO:K04685]
105298613  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
105298668  LAMC3; laminin subunit gamma-3 [KO:K06247]
105298702  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105299274  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105300023  RB1; retinoblastoma-associated protein [KO:K06618]
105300159  [KO:K04456] [EC:2.7.11.1]
105300252  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105300255  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
105300311  [KO:K06244]
105300342  LAMB4; laminin subunit beta-4 [KO:K06245]
105300344  LAMB1; laminin subunit beta-1 [KO:K05636]
105300424  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105300975  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
105301000  [KO:K14021]
105301022  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
105301330  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
105301331  COL4A2; collagen alpha-2(IV) chain isoform X1 [KO:K06237]
105301444  LAMA5; laminin subunit alpha-5 [KO:K06240]
105301455  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
105301762  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
105302177  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
105302419  LAMB2; laminin subunit beta-2 [KO:K06243]
105302420  [KO:K06243]
105302532  IKBKG; NF-kappa-B essential modulator [KO:K07210]
105302600  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105302792  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
105302941  RXRA; retinoic acid receptor RXR-alpha [KO:K08524]
105303008  ITGB1; integrin beta-1 [KO:K05719]
105303182  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105303529  ITGA2B; integrin alpha-IIb [KO:K06476]
105303899  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105304241  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
105304277  E2F1; transcription factor E2F1 [KO:K17454]
105304619  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
105305503  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
105307128  [KO:K04503]
105307139  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307393  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
105307445  SKP2; S-phase kinase-associated protein 2 isoform X2 [KO:K03875]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105307748  PTK2; focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
105307927  ITGA2; integrin alpha-2 isoform X1 [KO:K06481]
105308374  MAX; protein max isoform X1 [KO:K04453]
105308799  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105311216  [KO:K04685]
111728746  [KO:K14021]
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
pvp04110  Cell cycle
pvp04115  p53 signaling pathway
pvp04151  PI3K-Akt signaling pathway
pvp04210  Apoptosis
pvp04510  Focal adhesion
pvp04512  ECM-receptor interaction
KO pathway
ko05222   

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