KEGG   PATHWAY: tge05222
Entry
tge05222                    Pathway                                
Name
Small cell lung cancer - Theropithecus gelada (gelada)
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
tge05222  Small cell lung cancer
tge05222

Organism
Theropithecus gelada (gelada) [GN:tge]
Gene
112619529  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
112618120  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
112608151  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
112622109  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
112629339  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
112610199  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
112623750  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
112608708  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
112611273  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
112612483  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta isoform X1 [KO:K04402]
112613606  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
112622824  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
112606094  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
112625894  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
112611529  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
112620387  cytochrome c, somatic [KO:K08738]
112621297  cytochrome c [KO:K08738]
112622774  cytochrome c-like [KO:K08738]
112623008  cytochrome c-like [KO:K08738]
112608628  cytochrome c-like [KO:K08738]
112614550  cytochrome c-like [KO:K08738]
112625466  cytochrome c [KO:K08738]
112611588  cytochrome c-like [KO:K08738]
112626808  cytochrome c-like [KO:K08738]
112634215  cytochrome c-like [KO:K08738]
112605628  cytochrome c-like [KO:K08738]
112618713  cytochrome c-like [KO:K08738]
112634060  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
112628633  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
112622580  LOW QUALITY PROTEIN: caspase-3-like [KO:K02187] [EC:3.4.22.56]
112625066  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
112630275  MYC; myc proto-oncogene protein [KO:K04377]
112628931  MAX; protein max isoform X1 [KO:K04453]
112618957  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
112607789  CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685]
112634055  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
112620347  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
112605640  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
112607974  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
112636503  CKS1B; cyclin-dependent kinases regulatory subunit 1 isoform X2 [KO:K02219]
112625831  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
112634261  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
112633979  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
112629797  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
112612586  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
112610754  RB1; retinoblastoma-associated protein [KO:K06618]
112632890  E2F1; transcription factor E2F1 [KO:K17454]
112629771  E2F2; transcription factor E2F2 [KO:K09389]
112623737  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
112636054  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
112636055  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
112615476  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
112616409  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
112610842  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
112610843  COL4A1; collagen alpha-1(IV) chain isoform X1 [KO:K06237]
112622484  LAMA2; LOW QUALITY PROTEIN: laminin subunit alpha-2 [KO:K05637]
112611389  LAMA1; laminin subunit alpha-1 [KO:K05637]
112632455  LAMA5; laminin subunit alpha-5 [KO:K06240]
112611518  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
112622355  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
112620300  LAMB1; laminin subunit beta-1 isoform X1 [KO:K05636]
112618840  LAMB2; laminin subunit beta-2 [KO:K06243]
112606298  LAMB3; laminin subunit beta-3 [KO:K06244]
112620871  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
112622755  LAMC1; laminin subunit gamma-1 [KO:K05635]
112636862  LAMC2; laminin subunit gamma-2 [KO:K06246]
112608022  LAMC3; laminin subunit gamma-3 [KO:K06247]
112636080  FN1; fibronectin isoform X1 [KO:K05717]
112627002  ITGA2; integrin alpha-2 [KO:K06481]
112609387  ITGA2B; integrin alpha-IIb [KO:K06476]
112609718  ITGA3; integrin alpha-3 [KO:K06482]
112635986  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
112635941  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
112631395  ITGB1; integrin beta-1 [KO:K05719]
112630666  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
112618874  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112634042  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
112619294  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
112614522  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
112625914  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112612001  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
112631315  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]
112629473  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112609286  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112612288  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112632013  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
112629970  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
112616513  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
112616847  NF-kappa-B essential modulator-like [KO:K07210]
112628601  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
112624752  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
112605794  RELA; transcription factor p65 isoform X1 [KO:K04735]
112605791  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
112605792  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
112616539  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
112605321  BIRC8; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 8 [KO:K04725] [EC:2.3.2.27]
112617308  baculoviral IAP repeat-containing protein 7 [KO:K16061]
112617310  baculoviral IAP repeat-containing protein 7-like isoform X1 [KO:K16061]
112632856  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
112608030  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
112608018  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
112629252  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
112609875  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
112610017  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
112607412  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
112611851  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
112609895  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
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
tge04110  Cell cycle
tge04115  p53 signaling pathway
tge04151  PI3K-Akt signaling pathway
tge04210  Apoptosis
tge04510  Focal adhesion
tge04512  ECM-receptor interaction
KO pathway
ko05222   
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