KEGG   PATHWAY: ccad05222
Entry
ccad05222                   Pathway                                
Name
Small cell lung cancer - Cervus canadensis (wapiti)
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
ccad05222  Small cell lung cancer
ccad05222

Organism
Cervus canadensis (wapiti) [GN:ccad]
Gene
122424743  FHIT; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
122432566  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
122442371  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
122429967  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
122429874  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
122445826  TP53; cellular tumor antigen P53 [KO:K04451]
122429747  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
122440181  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
122432031  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
122436847  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
122421035  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
122430151  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
122450465  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
122442982  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
122425862  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
122438479  cytochrome c [KO:K08738]
122440592  cytochrome c [KO:K08738]
122432475  cytochrome c-like [KO:K08738]
122434040  cytochrome c [KO:K08738]
122435448  cytochrome c [KO:K08738]
122443337  cytochrome c-like [KO:K08738]
122453615  cytochrome c [KO:K08738]
122444772  cytochrome c-like [KO:K08738]
122454513  cytochrome c-like [KO:K08738]
122436938  cytochrome c-like [KO:K08738]
122423286  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
122452241  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
122432443  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
122451212  MYC; myc proto-oncogene protein [KO:K04377]
122449871  protein max [KO:K04453]
122443760  MAX; protein max isoform X1 [KO:K04453]
122452357  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
122452872  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
122427215  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
122438094  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
122430666  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
122432021  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
122432868  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
122454407  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
122423697  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
122427513  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
122421575  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
122450896  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
122447603  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
122448331  E2F1; transcription factor E2F1 [KO:K17454]
122426579  E2F2; transcription factor E2F2 [KO:K09389]
122429389  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
122447620  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
122447621  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
122426125  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
122426397  COL4A4; collagen alpha-4(IV) chain isoform X1 [KO:K06237]
122435152  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
122434442  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
122434014  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
122425783  LAMA1; laminin subunit alpha-1 [KO:K05637]
122448122  LAMA5; laminin subunit alpha-5 [KO:K06240]
122425623  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
122422681  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
122438320  LAMB1; laminin subunit beta-1 [KO:K05636]
122424462  laminin subunit beta-2 [KO:K06243]
122424593  laminin subunit beta-2-like [KO:K06243]
122452540  LAMB3; laminin subunit beta-3 [KO:K06244]
122438321  LAMB4; LOW QUALITY PROTEIN: laminin subunit beta-4 [KO:K06245]
122452508  LAMC1; laminin subunit gamma-1 [KO:K05635]
122452110  LAMC2; laminin subunit gamma-2 [KO:K06246]
122442281  LAMC3; laminin subunit gamma-3 isoform X1 [KO:K06247]
122426410  FN1; fibronectin isoform X1 [KO:K05717]
122454231  ITGA2; integrin alpha-2 [KO:K06481]
122440505  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
122443161  ITGA3; integrin alpha-3 [KO:K06482]
122453606  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
122453909  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
122447938  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
122451056  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
122451688  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122445271  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122444906  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122440740  PIK3R2; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122454626  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
122437038  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
122446193  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]
122420500  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122452448  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122455107  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122446045  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
122432633  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
122434540  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
122455294  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
122422050  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
122430633  RELA; transcription factor p65 isoform X1 [KO:K04735]
122449723  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
122449787  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
122434599  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
122448848  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
122448845  BCL2L1; bcl-2-like protein 1 [KO:K04570]
122449331  bcl-2-like protein 1 [KO:K04570]
122441342  bcl-2-like protein 1 [KO:K04570]
122431882  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
122442423  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
122454978  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
122448357  TRAF4; TNF receptor-associated factor 4 isoform X1 [KO:K09848]
122452144  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
122449806  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
122452326  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
122448629  NOS2; nitric oxide synthase, inducible isoform X1 [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
ccad04110  Cell cycle
ccad04115  p53 signaling pathway
ccad04151  PI3K-Akt signaling pathway
ccad04210  Apoptosis
ccad04510  Focal adhesion
ccad04512  ECM-receptor interaction
KO pathway
ko05222   
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