KEGG   PATHWAY: rro05222
Entry
rro05222                    Pathway                                

Name
Small cell lung cancer - Rhinopithecus roxellana (golden snub-nosed monkey)
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
rro05222  Small cell lung cancer
rro05222

Organism
Rhinopithecus roxellana (golden snub-nosed monkey) [GN:rro]
Gene
104671818  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
104658073  RARB; retinoic acid receptor beta isoform X2 [KO:K08528]
104669710  RXRA; retinoic acid receptor RXR-alpha isoform X3 [KO:K08524]
104657982  RXRB; retinoic acid receptor RXR-beta isoform X3 [KO:K08525]
104670175  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
104661662  TP53; cellular tumor antigen p53 [KO:K04451]
104682880  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
104671382  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
104657306  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
104656307  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
104666540  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
104658958  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
104668405  DDB2; DNA damage-binding protein 2 [KO:K10140]
104653753  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
104682248  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
104661761  cytochrome c-like [KO:K08738]
104679886  cytochrome c [KO:K08738]
104672188  cytochrome c [KO:K08738]
104681924  cytochrome c-like [KO:K08738]
115898126  cytochrome c-like [KO:K08738]
115894533  cytochrome c-like [KO:K08738]
115893266  cytochrome c-like [KO:K08738]
115893541  cytochrome c-like [KO:K08738]
115899152  cytochrome c-like [KO:K08738]
104656342  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
104677696  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
104666783  caspase-3-like [KO:K02187] [EC:3.4.22.56]
104673791  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
104674798  MYC; myc proto-oncogene protein [KO:K04377]
104678435  MAX; protein max isoform X1 [KO:K04453]
104668148  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X2 [KO:K10500]
104654271  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
104682344  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
104682750  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
104677168  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
104660852  cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
104668525  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
104663482  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
115900272  cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
104662024  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
104668343  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
104673700  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
104660331  CCNE2; G1/S-specific cyclin-E2 isoform X2 [KO:K06626]
104656155  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
104662760  RB1; retinoblastoma-associated protein [KO:K06618]
104660298  E2F1; transcription factor E2F1 [KO:K17454]
104656129  E2F2; LOW QUALITY PROTEIN: transcription factor E2F2 [KO:K09389]
104654803  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
104679242  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
104658850  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
104671965  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
104671966  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
104679243  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
104665145  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
104670221  LAMA1; LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637]
104655298  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
104678039  laminin subunit alpha-3 isoform X2 [KO:K06240]
104663822  LAMA5; LOW QUALITY PROTEIN: laminin subunit alpha-5 [KO:K06240]
104659760  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
104677415  LAMB1; laminin subunit beta-1 isoform X1 [KO:K05636]
104667469  LAMB2; laminin subunit beta-2 [KO:K06243]
104664167  LAMB3; laminin subunit beta-3 [KO:K06244]
104672365  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
104666795  LAMC1; laminin subunit gamma-1 [KO:K05635]
104666798  LAMC2; laminin subunit gamma-2 [KO:K06246]
104660568  LAMC3; laminin subunit gamma-3 [KO:K06247]
104669238  FN1; fibronectin isoform X1 [KO:K05717]
104672477  ITGA2; integrin alpha-2 [KO:K06481]
104654717  ITGA2B; integrin alpha-IIb [KO:K06476]
104680261  ITGA3; integrin alpha-3 [KO:K06482]
104673514  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
104667754  ITGAV; integrin alpha-V isoform X2 [KO:K06487]
104663301  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
104679749  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
104663050  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
104665061  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
104670605  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
104662124  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
104675620  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104680672  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104675158  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]
104673041  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104676121  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104654186  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
115893905  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104656469  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
104666046  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
104667046  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
104679802  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
104662315  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
104664815  RELA; transcription factor p65 [KO:K04735]
104674657  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
104674658  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X2 [KO:K16060]
104655196  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
104663843  BIRC7; baculoviral IAP repeat-containing protein 7 isoform X1 [KO:K16061]
104653720  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
104669131  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
104669650  TRAF2; TNF receptor-associated factor 2 isoform X2 [KO:K03173] [EC:2.3.2.27]
104654431  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
104674107  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
104669508  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
104658364  TRAF6; LOW QUALITY PROTEIN: TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
104664377  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
104669357  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
rro04110  Cell cycle
rro04115  p53 signaling pathway
rro04151  PI3K-Akt signaling pathway
rro04210  Apoptosis
rro04510  Focal adhesion
rro04512  ECM-receptor interaction
KO pathway
ko05222   
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