KEGG   PATHWAY: puc05222
Entry
puc05222                    Pathway                                
Name
Small cell lung cancer - Panthera uncia (snow leopard)
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
puc05222  Small cell lung cancer
puc05222

Organism
Panthera uncia (snow leopard) [GN:puc]
Gene
125929536  bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
125921369  retinoic acid receptor beta isoform X1 [KO:K08528]
125922972  retinoic acid receptor RXR-alpha [KO:K08524]
125938378  retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
125925934  retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
125927023  LOW QUALITY PROTEIN: cellular tumor antigen p53 [KO:K04451]
125938307  cyclin-dependent kinase inhibitor 1 [KO:K06625]
125929753  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
125930526  growth arrest and DNA damage-inducible protein GADD45 beta isoform X1 [KO:K04402]
125912521  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
125915138  apoptosis regulator BAX isoform X1 [KO:K02159]
125938359  bcl-2 homologous antagonist/killer [KO:K14021]
125933993  DNA damage-binding protein 2 isoform X1 [KO:K10140]
125935748  DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
125914709  apoptosis regulator Bcl-2 [KO:K02161]
125929995  cytochrome c [KO:K08738]
125933126  LOW QUALITY PROTEIN: cytochrome c-like [KO:K08738]
125920151  cytochrome c-like [KO:K08738]
125920269  cytochrome c-like [KO:K08738]
125921158  cytochrome c-like [KO:K08738]
125919454  apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
125913078  caspase-9 [KO:K04399] [EC:3.4.22.62]
125923904  caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
125924410  myc proto-oncogene protein [KO:K04377]
125908721  protein max isoform X1 [KO:K04453]
125913062  zinc finger and BTB domain-containing protein 17 [KO:K10500]
125915304  cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685]
125919257  cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
125930419  cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
125930010  G1/S-specific cyclin-D1 [KO:K04503]
125929638  cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
125925733  cyclin-dependent kinases regulatory subunit 1 isoform X1 [KO:K02219]
125934645  S-phase kinase-associated protein 2 [KO:K03875]
125918841  cyclin-dependent kinase inhibitor 1B [KO:K06624]
125919210  cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
125924535  G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
125917277  G1/S-specific cyclin-E1 [KO:K06626]
125917289  G1/S-specific cyclin-E1 [KO:K06626]
125933773  retinoblastoma-associated protein isoform X1 [KO:K06618]
125936106  transcription factor E2F1 [KO:K17454]
125912975  transcription factor E2F2 [KO:K09389]
125908499  transcription factor E2F3 [KO:K06620]
125931891  collagen alpha-6(IV) chain [KO:K06237]
125931892  collagen alpha-5(IV) chain [KO:K06237]
125933953  collagen alpha-2(IV) chain [KO:K06237]
125934049  collagen alpha-1(IV) chain [KO:K06237]
125911119  collagen alpha-4(IV) chain [KO:K06237]
125911120  collagen alpha-3(IV) chain [KO:K06237]
125914808  LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637]
125937984  laminin subunit alpha-2 [KO:K05637]
125914386  laminin subunit alpha-3 isoform X1 [KO:K06240]
125936426  laminin subunit alpha-5 [KO:K06240]
125937961  laminin subunit alpha-4 isoform X1 [KO:K06241]
125929828  laminin subunit beta-1 [KO:K05636]
125929332  laminin subunit beta-2 [KO:K06243]
125925325  laminin subunit beta-3 [KO:K06244]
125929830  laminin subunit beta-4 [KO:K06245]
125925244  laminin subunit gamma-1 [KO:K05635]
125925243  laminin subunit gamma-2 [KO:K06246]
125922657  laminin subunit gamma-3 [KO:K06247]
125911221  fibronectin isoform X1 [KO:K05717]
125918095  integrin alpha-2 [KO:K06481]
125918098  integrin alpha-2 [KO:K06481]
125926633  integrin alpha-IIb [KO:K06476]
125926426  integrin alpha-3 [KO:K06482]
125911548  integrin alpha-6 isoform X1 [KO:K06485]
125911491  integrin alpha-V [KO:K06487]
125918681  integrin beta-1 isoform X1 [KO:K05719]
125924709  focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
125921850  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
125913143  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
125921289  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
125913493  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
125935698  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
125929237  phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
125933550  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]
125915806  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125909102  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125925091  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125932873  inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
125923306  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
125932096  NF-kappa-B essential modulator isoform X1 [KO:K07210]
125909567  NF-kappa-B inhibitor alpha [KO:K04734]
125923687  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
125912163  transcription factor p65 [KO:K04735]
125929805  baculoviral IAP repeat-containing protein 2 [KO:K16060]
125917180  baculoviral IAP repeat-containing protein 3-like isoform X1 [KO:K16060]
125918027  baculoviral IAP repeat-containing protein 3-like isoform X1 [KO:K16060]
125932285  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
125936284  baculoviral IAP repeat-containing protein 7 [KO:K16061]
125936704  bcl-2-like protein 1 isoform X1 [KO:K04570]
125920844  TNF receptor-associated factor 1 isoform X1 [KO:K03172]
125923516  TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
125909139  TNF receptor-associated factor 3 isoform X1 [KO:K03174]
125926832  TNF receptor-associated factor 4 [KO:K09848]
125925301  TNF receptor-associated factor 5 isoform X1 [KO:K09849]
125934537  TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
125925212  prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
125927474  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
puc04110  Cell cycle
puc04115  p53 signaling pathway
puc04151  PI3K-Akt signaling pathway
puc04210  Apoptosis
puc04510  Focal adhesion
puc04512  ECM-receptor interaction
KO pathway
ko05222   
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