KEGG   PATHWAY: nasi05222
Entry
nasi05222                   Pathway                                
Name
Small cell lung cancer - Neophocaena asiaeorientalis asiaeorientalis (Yangtze finless porpoise)
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
nasi05222  Small cell lung cancer
nasi05222

Organism
Neophocaena asiaeorientalis asiaeorientalis (Yangtze finless porpoise) [GN:nasi]
Gene
112400625  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
112411691  retinoic acid receptor beta-like [KO:K08528]
112395109  RARB; retinoic acid receptor beta [KO:K08528]
112411563  RXRA; retinoic acid receptor RXR-alpha [KO:K08524]
112413837  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
112397710  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
112401891  TP53; cellular tumor antigen p53 [KO:K04451]
112414074  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
112396403  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
112392793  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
112390848  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
112415661  BAX; apoptosis regulator BAX [KO:K02159]
112414038  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
112402084  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
112391413  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
112406137  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
112409526  cytochrome c-like [KO:K08738]
112396438  cytochrome c-like [KO:K08738]
112403640  LOW QUALITY PROTEIN: cytochrome c-like [KO:K08738]
112406320  cytochrome c [KO:K08738]
112414113  LOW QUALITY PROTEIN: cytochrome c-like [KO:K08738]
112394162  cytochrome c-like [KO:K08738]
112391536  cytochrome c 2 [KO:K08738]
112409026  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
112402819  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
112409662  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
112397143  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
112403389  MAX; protein max isoform X1 [KO:K04453]
112402816  ZBTB17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
112415058  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
112394295  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
112414528  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
112402178  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
112401783  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
112390854  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
112406027  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
112391736  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
112394072  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
112407307  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
112392336  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
112406557  RB1; retinoblastoma-associated protein [KO:K06618]
112398484  E2F1; transcription factor E2F1 [KO:K17454]
112414298  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
112396632  E2F3; transcription factor E2F3 [KO:K06620]
112402080  COL4A5; collagen alpha-5(IV) chain [KO:K06237]
112402095  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
112396748  COL4A3; collagen alpha-3(IV) chain isoform X1 [KO:K06237]
112396749  COL4A4; collagen alpha-4(IV) chain isoform X1 [KO:K06237]
112405545  COL4A2; collagen alpha-2(IV) chain isoform X1 [KO:K06237]
112405565  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
112409100  LAMA2; laminin subunit alpha-2 [KO:K05637]
112412147  LAMA1; laminin subunit alpha-1 [KO:K05637]
112402951  LAMA5; LOW QUALITY PROTEIN: laminin subunit alpha-5 [KO:K06240]
112408327  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
112396971  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
112397922  LAMB1; laminin subunit beta-1 [KO:K05636]
112394660  LAMB2; laminin subunit beta-2 [KO:K06243]
112403506  LAMB3; laminin subunit beta-3 [KO:K06244]
112391177  LAMC1; laminin subunit gamma-1 [KO:K05635]
112391277  LAMC2; laminin subunit gamma-2 [KO:K06246]
112411540  LAMC3; laminin subunit gamma-3 [KO:K06247]
112411833  FN1; fibronectin isoform X1 [KO:K05717]
112396551  ITGA2; integrin alpha-2 [KO:K06481]
112410314  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
112398462  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
112391504  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
112403267  ITGAV; integrin alpha-V [KO:K06487]
112413437  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
112397030  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
112402798  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
112403325  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
112406349  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112404930  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112400438  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
112414874  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
112399575  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]
112405757  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112408453  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112415459  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112392983  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
112413114  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
112400454  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
112411167  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
112393728  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
112402272  RELA; transcription factor p65 [KO:K04735]
112409959  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
112409963  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
112401089  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
112402946  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
112398447  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
112411542  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
112411269  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
112408757  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
112394521  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
112403568  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
112404544  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
112403598  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
112394495  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
nasi04110  Cell cycle
nasi04115  p53 signaling pathway
nasi04151  PI3K-Akt signaling pathway
nasi04210  Apoptosis
nasi04510  Focal adhesion
nasi04512  ECM-receptor interaction
KO pathway
ko05222   
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