KEGG   PATHWAY: nle05222
Entry
nle05222                    Pathway                                
Name
Small cell lung cancer - Nomascus leucogenys (northern white-cheeked gibbon)
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
nle05222  Small cell lung cancer
nle05222

Organism
Nomascus leucogenys (northern white-cheeked gibbon) [GN:nle]
Gene
100587886  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
100596579  RARB; retinoic acid receptor beta isoform X2 [KO:K08528]
100585339  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
100580742  RXRB; retinoic acid receptor RXR-beta isoform X2 [KO:K08525]
100592610  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
100583326  TP53; cellular tumor antigen p53 [KO:K04451]
100599083  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100593432  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100583800  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
115830865  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100593013  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
100588483  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
100605065  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
100598341  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
100599011  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100603746  cytochrome c-like [KO:K08738]
100600457  cytochrome c-like [KO:K08738]
100580069  cytochrome c [KO:K08738]
100598207  cytochrome c-like [KO:K08738]
100599727  cytochrome c-like [KO:K08738]
101179576  cytochrome c-like [KO:K08738]
100604294  cytochrome c-like [KO:K08738]
100590369  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
100597173  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
100585064  CASP3; caspase-3 isoform X3 [KO:K02187] [EC:3.4.22.56]
100589322  MYC; myc proto-oncogene protein [KO:K04377]
100601755  MAX; protein max isoform X2 [KO:K04453]
100589356  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
100593298  CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685]
100594967  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100602542  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100605736  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100590950  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
100580794  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
100586655  SKP2; S-phase kinase-associated protein 2 isoform X2 [KO:K03875]
100589956  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100592796  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
100607751  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
100602200  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
100588629  RB1; retinoblastoma-associated protein [KO:K06618]
100601097  E2F1; transcription factor E2F1 [KO:K17454]
100583853  E2F2; transcription factor E2F2 [KO:K09389]
100594018  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
100598507  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
100587255  COL4A6; collagen alpha-6(IV) chain isoform X3 [KO:K06237]
100584285  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
100603791  COL4A1; collagen alpha-1(IV) chain isoform X1 [KO:K06237]
100588259  COL4A5; collagen alpha-5(IV) chain [KO:K06237]
100598848  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
100591959  LAMA1; laminin subunit alpha-1 [KO:K05637]
100583654  LAMA2; laminin subunit alpha-2 [KO:K05637]
100601935  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
100581144  LAMA5; laminin subunit alpha-5 isoform X1 [KO:K06240]
100587786  LAMA4; laminin subunit alpha-4 [KO:K06241]
100581721  LAMB1; laminin subunit beta-1 [KO:K05636]
100591482  LAMB2; laminin subunit beta-2 isoform X1 [KO:K06243]
100593136  LAMB3; laminin subunit beta-3 [KO:K06244]
100581377  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
100607126  LAMC1; laminin subunit gamma-1 [KO:K05635]
100581925  LAMC2; laminin subunit gamma-2 [KO:K06246]
100602023  LAMC3; laminin subunit gamma-3 [KO:K06247]
100601303  FN1; fibronectin isoform X2 [KO:K05717]
100588661  ITGA2; integrin alpha-2 isoform X1 [KO:K06481]
100601385  ITGA2B; integrin alpha-IIb [KO:K06476]
100596503  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
100600735  ITGA6; integrin alpha-6 isoform X2 [KO:K06485]
100604485  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
100595108  ITGB1; integrin beta-1 [KO:K05719]
100588218  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100580872  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100584384  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100605788  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100591270  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100599301  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100605147  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]
100604331  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100587864  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100587109  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100596225  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100588081  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
100603768  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
100599351  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100581655  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100588439  RELA; transcription factor p65 [KO:K04735]
100579740  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
100580307  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
100597865  XIAP; E3 ubiquitin-protein ligase XIAP isoform X4 [KO:K04725] [EC:2.3.2.27]
100586363  BIRC7; baculoviral IAP repeat-containing protein 7 isoform X1 [KO:K16061]
100595330  BCL2L1; bcl-2-like protein 1 [KO:K04570]
100605879  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
100590721  TRAF2; TNF receptor-associated factor 2 isoform X2 [KO:K03173] [EC:2.3.2.27]
100606382  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
100607896  TRAF4; TNF receptor-associated factor 4 isoform X1 [KO:K09848]
100601779  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
100595327  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
100591090  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
100589003  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
nle04110  Cell cycle
nle04115  p53 signaling pathway
nle04151  PI3K-Akt signaling pathway
nle04210  Apoptosis
nle04510  Focal adhesion
nle04512  ECM-receptor interaction
KO pathway
ko05222   
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