KEGG   PATHWAY: mni05222
Entry
mni05222                    Pathway                                
Name
Small cell lung cancer - Macaca nemestrina (pig-tailed macaque)
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
mni05222  Small cell lung cancer
mni05222

Organism
Macaca nemestrina (pig-tailed macaque) [GN:mni]
Gene
105483059  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
105488933  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
105471885  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
105474442  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
105492958  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
105473688  TP53; cellular tumor antigen p53 [KO:K04451]
105474528  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105485789  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105498437  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
105498812  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105478665  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
105474465  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
105471678  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
105475129  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
105477002  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
105475711  cytochrome c [KO:K08738]
105495842  cytochrome c-like [KO:K08738]
105477037  cytochrome c-like [KO:K08738]
105486922  cytochrome c-like [KO:K08738]
105477715  cytochrome c-like [KO:K08738]
105487609  cytochrome c-like [KO:K08738]
105497820  cytochrome c-like [KO:K08738]
105491771  cytochrome c-like [KO:K08738]
112428088  cytochrome c-like [KO:K08738]
105485043  cytochrome c-like [KO:K08738]
105495023  cytochrome c-like [KO:K08738]
105463369  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
105473212  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
105466747  CASP3; LOW QUALITY PROTEIN: caspase-3 [KO:K02187] [EC:3.4.22.56]
105492342  caspase-3-like isoform X1 [KO:K02187] [EC:3.4.22.56]
105492792  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
105473705  MAX; protein max isoform X2 [KO:K04453]
105473222  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
105498411  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
105474081  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
105475503  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
105469727  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
105497985  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
105498798  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
105482768  cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
105473080  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
105482108  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
105474169  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105497230  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
105487658  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
105490695  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
105496223  E2F1; transcription factor E2F1 [KO:K17454]
105494424  E2F2; LOW QUALITY PROTEIN: transcription factor E2F2 [KO:K09389]
105482518  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105485298  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
105485301  COL4A1; LOW QUALITY PROTEIN: collagen alpha-1(IV) chain [KO:K06237]
105473978  COL4A4; collagen alpha-4(IV) chain isoform X1 [KO:K06237]
105473981  COL4A3; collagen alpha-3(IV) chain isoform X1 [KO:K06237]
105490453  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
105490456  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
105465590  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
105478856  LAMA1; laminin subunit alpha-1 isoform X2 [KO:K05637]
105465071  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
105470533  LAMA5; laminin subunit alpha-5 [KO:K06240]
105499731  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
105475300  LAMB1; laminin subunit beta-1 [KO:K05636]
105480428  LAMB2; laminin subunit beta-2 [KO:K06243]
105484900  LAMB3; laminin subunit beta-3 [KO:K06244]
105475298  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
105484563  LAMC1; laminin subunit gamma-1 isoform X1 [KO:K05635]
105484564  LAMC2; laminin subunit gamma-2 isoform X1 [KO:K06246]
105464043  LAMC3; LOW QUALITY PROTEIN: laminin subunit gamma-3 [KO:K06247]
105481166  FN1; fibronectin isoform X1 [KO:K05717]
105499361  ITGA2; integrin alpha-2 [KO:K06481]
105469039  ITGA2B; integrin alpha-IIb [KO:K06476]
105472360  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
105483230  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
105468297  ITGAV; LOW QUALITY PROTEIN: integrin alpha-V [KO:K06487]
105479922  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
105488506  PTK2; focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
105478978  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105489973  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105469947  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105475205  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105488082  PIK3R2; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105494953  PIK3R3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
105480917  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]
105474669  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105489842  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105495343  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105478402  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
105476527  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
105471007  LOW QUALITY PROTEIN: NF-kappa-B essential modulator-like [KO:K07210]
105477978  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105486337  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X3 [KO:K02580]
105469585  RELA; transcription factor p65 isoform X1 [KO:K04735]
105493720  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
105493721  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
105468434  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
105470503  BIRC7; baculoviral IAP repeat-containing protein 7 isoform X1 [KO:K16061]
105496162  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
105487148  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
105471953  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
105467377  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
105476400  TRAF4; TNF receptor-associated factor 4 isoform X1 [KO:K09848]
105493576  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
105471571  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
105484600  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
105476942  NOS2; LOW QUALITY PROTEIN: 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
mni04110  Cell cycle
mni04115  p53 signaling pathway
mni04151  PI3K-Akt signaling pathway
mni04210  Apoptosis
mni04510  Focal adhesion
mni04512  ECM-receptor interaction
KO pathway
ko05222   
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