KEGG   PATHWAY: pcw05222
Entry
pcw05222                    Pathway                                

Name
Small cell lung cancer - Phascolarctos cinereus (koala)
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
pcw05222  Small cell lung cancer
pcw05222

Organism
Phascolarctos cinereus (koala) [GN:pcw]
Gene
110201683  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
110197316  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
110205364  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
110199336  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
110209882  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
110194271  TP53; cellular tumor antigen p53 [KO:K04451]
110217257  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
110212964  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
110223449  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110195907  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110219776  BAX; apoptosis regulator BAX [KO:K02159]
110217311  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
110223919  DDB2; LOW QUALITY PROTEIN: DNA damage-binding protein 2 [KO:K10140]
110216585  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
110214751  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
110218411  cytochrome c-like [KO:K08738]
110218003  cytochrome c-like [KO:K08738]
110203137  cytochrome c-like [KO:K08738]
110213139  cytochrome c [KO:K08738]
110221734  APAF1; LOW QUALITY PROTEIN: apoptotic protease-activating factor 1 [KO:K02084]
110198824  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
110222594  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
110216083  MYC; myc proto-oncogene protein [KO:K04377]
110220610  MAX; protein max isoform X1 [KO:K04453]
110198716  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
110201194  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
110210989  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
110209152  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
110197171  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
110223828  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
110211967  CKS1B; cyclin-dependent kinases regulatory subunit 1 isoform X1 [KO:K02219]
110214774  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
110218707  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
110210908  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
110207433  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
110195790  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
110213446  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
110216806  E2F1; transcription factor E2F1 [KO:K17454]
110206051  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
110208713  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
110197222  COL4A3; LOW QUALITY PROTEIN: collagen alpha-3(IV) chain [KO:K06237]
110200243  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
110194741  COL4A5; collagen alpha-5(IV) chain [KO:K06237]
110196697  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
110196698  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
110208858  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
110199966  LAMA1; LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637]
110205178  LAMA5; LOW QUALITY PROTEIN: laminin subunit alpha-5 [KO:K06240]
110195785  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
110222892  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
110207016  LAMB1; laminin subunit beta-1 [KO:K05636]
110216959  LOW QUALITY PROTEIN: laminin subunit beta-2-like [KO:K06243]
110216962  LAMB2; laminin subunit beta-2 [KO:K06243]
110222728  LAMB3; laminin subunit beta-3 [KO:K06244]
110206931  LAMB4; LOW QUALITY PROTEIN: laminin subunit beta-4 [KO:K06245]
110206842  LAMC1; laminin subunit gamma-1 [KO:K05635]
110206843  LAMC2; laminin subunit gamma-2 [KO:K06246]
110198932  LAMC3; laminin subunit gamma-3 [KO:K06247]
110219415  FN1; fibronectin isoform X1 [KO:K05717]
110215432  ITGA2; integrin alpha-2 isoform X1 [KO:K06481]
110215866  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
110215841  ITGA3; integrin alpha-3 [KO:K06482]
110211575  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
110201716  ITGAV; integrin alpha-V [KO:K06487]
110211245  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
110194600  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
110204454  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110208219  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110199476  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
110223395  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110216530  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110209293  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
110199935  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]
110205475  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110202713  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110203042  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110213919  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
110196387  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110200334  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
110211795  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
110209686  NFKB1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580]
110195563  RELA; transcription factor p65 isoform X1 [KO:K04735]
110215022  baculoviral IAP repeat-containing protein 2-like isoform X1 [KO:K16060]
110215023  baculoviral IAP repeat-containing protein 2-like isoform X1 [KO:K16060]
110200954  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
110205196  BIRC7; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 7 [KO:K16061]
110211412  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
110211345  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
110205309  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
110197337  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
110192193  TRAF4; TNF receptor-associated factor 4 isoform X1 [KO:K09848]
110222706  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
110192620  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
110206875  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
110192171  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
pcw04110  Cell cycle
pcw04115  p53 signaling pathway
pcw04151  PI3K-Akt signaling pathway
pcw04210  Apoptosis
pcw04510  Focal adhesion
pcw04512  ECM-receptor interaction
KO pathway
ko05222   
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