KEGG   PATHWAY: shr05222
Entry
shr05222                    Pathway                                
Name
Small cell lung cancer - Sarcophilus harrisii (Tasmanian devil)
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
shr05222  Small cell lung cancer
shr05222

Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
100923843  FHIT; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
100928834  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
100926708  RXRA; retinoic acid receptor RXR-alpha isoform X3 [KO:K08524]
100914649  RXRB; retinoic acid receptor RXR-beta isoform X2 [KO:K08525]
100932014  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
100922473  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
100926666  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100926902  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100920439  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
116423727  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100916731  BAK1; bcl-2 homologous antagonist/killer isoform X2 [KO:K14021]
100916232  DDB2; DNA damage-binding protein 2 [KO:K10140]
100923657  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
100934666  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100919671  cytochrome c 2 [KO:K08738]
111721251  cytochrome c [KO:K08738]
100932636  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
100931481  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
100922757  caspase-3-like [KO:K02187] [EC:3.4.22.56]
100922500  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100921308  MYC; myc proto-oncogene protein [KO:K04377]
100919026  MAX; protein max isoform X5 [KO:K04453]
100928371  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
100932899  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100924154  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100917462  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100917592  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
100915745  uncharacterized protein LOC100915745 [KO:K02219]
100915218  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
100928055  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
100925631  CDK2; cyclin-dependent kinase 2 isoform X4 [KO:K02206] [EC:2.7.11.22]
100920942  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
100924454  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
100914196  RB1; retinoblastoma-associated protein [KO:K06618]
116421696  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
100921594  E2F2; transcription factor E2F2 [KO:K09389]
100934669  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
100917328  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
100923249  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
100923506  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
100931618  COL4A5; collagen alpha-5(IV) chain [KO:K06237]
100917586  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
100925578  LAMA1; laminin subunit alpha-1 [KO:K05637]
100924495  LAMA2; laminin subunit alpha-2 isoform X4 [KO:K05637]
100924531  LAMA5; laminin subunit alpha-5 [KO:K06240]
100934145  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
100926054  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
100929086  LAMB1; laminin subunit beta-1 [KO:K05636]
100931469  laminin subunit beta-2 [KO:K06243]
111719421  laminin subunit beta-2-like [KO:K06243]
100922990  LAMB3; LOW QUALITY PROTEIN: laminin subunit beta-3 [KO:K06244]
100930114  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
100921255  LAMC1; laminin subunit gamma-1 [KO:K05635]
100921523  LAMC2; laminin subunit gamma-2 [KO:K06246]
100935179  LAMC3; laminin subunit gamma-3 isoform X1 [KO:K06247]
100927509  FN1; fibronectin isoform X4 [KO:K05717]
105749727  ITGA2; integrin alpha-2 [KO:K06481]
100932021  ITGA2B; integrin alpha-IIb [KO:K06476]
100928379  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
100929219  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
100929053  ITGAV; integrin alpha-V [KO:K06487]
100913968  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
100933019  PTK2; focal adhesion kinase 1 isoform X6 [KO:K05725] [EC:2.7.10.2]
100929811  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100932099  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105749979  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100926892  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100924976  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
100935230  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100927199  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]
100917987  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100913262  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100925440  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100913624  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100928932  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
100926701  IKBKG; NF-kappa-B essential modulator isoform X3 [KO:K07210]
100919027  NFKBIA; LOW QUALITY PROTEIN: NF-kappa-B inhibitor alpha [KO:K04734]
100917619  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100932473  RELA; transcription factor p65 [KO:K04735]
100914028  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
100933131  baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
100928240  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100918596  BIRC7; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 7 [KO:K16061]
100915548  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
100932053  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
100934749  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
100926344  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
100932711  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
100926831  TRAF5; TNF receptor-associated factor 5 isoform X2 [KO:K09849]
100922331  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100926756  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
100927789  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
shr04110  Cell cycle
shr04115  p53 signaling pathway
shr04151  PI3K-Akt signaling pathway
shr04210  Apoptosis
shr04510  Focal adhesion
shr04512  ECM-receptor interaction
KO pathway
ko05222   
LinkDB

DBGET integrated database retrieval system