KEGG   PATHWAY: rbb05222
Entry
rbb05222                    Pathway                                
Name
Small cell lung cancer - Rhinopithecus bieti (black 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
rbb05222  Small cell lung cancer
rbb05222

Disease
H00013  Small cell lung cancer
Organism
Rhinopithecus bieti (black snub-nosed monkey) [GN:rbb]
Gene
108512065  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
108512498  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108512689  [KO:K02187] [EC:3.4.22.56]
108512695  LAMC1; laminin subunit gamma-1 [KO:K05635]
108512736  LAMC2; laminin subunit gamma-2 [KO:K06246]
108513078  POLK; LOW QUALITY PROTEIN: DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
108513168  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
108513926  LAMC3; LOW QUALITY PROTEIN: laminin subunit gamma-3 [KO:K06247]
108514076  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
108514077  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
108514363  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
108514953  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
108515877  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
108516053  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
108516259  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
108516444  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
108518784  IKBKG; NF-kappa-B essential modulator [KO:K07210]
108519636  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
108521880  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108521962  DDB2; DNA damage-binding protein 2 [KO:K10140]
108522131  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
108522273  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
108522717  [KO:K06237]
108522903  ITGA2; integrin alpha-2 [KO:K06481]
108523178  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
108523439  [KO:K08738]
108523624  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
108523928  LAMA1; laminin subunit alpha-1 isoform X1 [KO:K05637]
108524009  [KO:K08738]
108524131  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
108524262  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
108524269  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
108524397  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
108524923  [KO:K08738]
108526412  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
108526816  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
108527002  LAMB2; laminin subunit beta-2 [KO:K06243]
108527057  COL4A1; LOW QUALITY PROTEIN: collagen alpha-1(IV) chain [KO:K06237]
108527058  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
108527540  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]
108528336  CDKN1A; LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1 [KO:K06625]
108528490  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
108528761  MYC; myc proto-oncogene protein [KO:K04377]
108529400  ITGB1; integrin beta-1 [KO:K05719]
108529671  [KO:K02219]
108530087  [KO:K08738]
108530161  [KO:K09848]
108530341  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
108530611  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
108530701  RB1; retinoblastoma-associated protein [KO:K06618]
108531451  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
108532191  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
108532236  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
108532817  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
108532870  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
108532915  [KO:K08738]
108532960  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
108533038  E2F1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
108533297  [KO:K08738]
108534276  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108534366  LAMA2; laminin subunit alpha-2 [KO:K05637]
108535053  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
108535077  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
108535245  LAMA5; LOW QUALITY PROTEIN: laminin subunit alpha-5 [KO:K06240]
108535289  BIRC7; baculoviral IAP repeat-containing protein 7 isoform X1 [KO:K16061]
108535417  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
108535521  [KO:K08738]
108535559  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
108535636  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
108536287  [KO:K08738]
108536899  LAMA3; laminin subunit alpha-3 [KO:K06240]
108537064  CDKN2B; LOW QUALITY PROTEIN: cyclin-dependent kinase 4 inhibitor B [KO:K04685]
108537107  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
108538378  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
108538448  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
108538612  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
108538728  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
108538745  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
108538749  COL4A4; collagen alpha-4(IV) chain isoform X1 [KO:K06237]
108538827  [KO:K08738]
108539069  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108539355  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108539549  LAMB3; laminin subunit beta-3 [KO:K06244]
108539896  CCNE2; LOW QUALITY PROTEIN: G1/S-specific cyclin-E2 [KO:K06626]
108539936  TRAF4; LOW QUALITY PROTEIN: TNF receptor-associated factor 4 [KO:K09848]
108539959  NOS2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
108540287  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
108540465  LAMB1; laminin subunit beta-1 [KO:K05636]
108540493  [KO:K06245]
108540719  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
108541175  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
108542424  MAX; protein max isoform X1 [KO:K04453]
108542901  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
108543072  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
108543178  FN1; fibronectin isoform X1 [KO:K05717]
108543462  APAF1; LOW QUALITY PROTEIN: apoptotic protease-activating factor 1 [KO:K02084]
108543519  RELA; transcription factor p65 [KO:K04735]
108543621  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
108544148  PTK2; focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
108544591  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
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
rbb04110  Cell cycle
rbb04115  p53 signaling pathway
rbb04151  PI3K-Akt signaling pathway
rbb04210  Apoptosis
rbb04510  Focal adhesion
rbb04512  ECM-receptor interaction
KO pathway
ko05222   

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