KEGG   PATHWAY: bacu05222
Entry
bacu05222                   Pathway                                
Name
Small cell lung cancer - Balaenoptera acutorostrata scammoni (minke whale)
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
bacu05222  Small cell lung cancer
bacu05222

Organism
Balaenoptera acutorostrata scammoni (minke whale) [GN:bacu]
Gene
103003452  FHIT; fragile histidine triad [KO:K01522] [EC:3.6.1.29]
103004858  RARB; retinoic acid receptor beta [KO:K08528]
103005517  RXRA; retinoid X receptor alpha [KO:K08524]
103006710  RXRB; retinoid X receptor beta [KO:K08525]
103017600  RXRG; retinoid X receptor gamma [KO:K08526]
103003426  TP53; tumor protein p53 [KO:K04451]
103005082  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
103012188  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
103016967  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
103020367  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
103019528  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
102999845  putative Bcl-2 homologous antagonist/killer 2-like [KO:K14021]
103017537  DDB2; damage specific DNA binding protein 2 [KO:K10140]
103009875  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
103015542  BCL2; BCL2, apoptosis regulator [KO:K02161]
103017780  cytochrome c 2-like [KO:K08738]
102999215  cytochrome c-like [KO:K08738]
103004375  cytochrome c-like [KO:K08738]
103003361  cytochrome c-like [KO:K08738]
103006029  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
103010071  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
103019939  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
103016933  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102999653  MAX; MYC associated factor X [KO:K04453]
103010937  ZBTB17; zinc finger and BTB domain containing 17 [KO:K10500]
103011925  CDKN2B; cyclin dependent kinase inhibitor 2B [KO:K04685]
103000540  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103010593  cyclin-dependent kinase 4-like [KO:K02089] [EC:2.7.11.22]
103011327  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103013404  CCND1; cyclin D1 [KO:K04503]
103010156  CKS2; CDC28 protein kinase regulatory subunit 2 [KO:K02219]
103015109  CKS1B; CDC28 protein kinase regulatory subunit 1B [KO:K02219]
103007736  SKP2; S-phase kinase associated protein 2 [KO:K03875]
103001464  CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
103012976  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
103008660  CCNE1; cyclin E1 [KO:K06626]
102997538  CCNE2; cyclin E2 [KO:K06626]
103013752  RB1; RB transcriptional corepressor 1 [KO:K06618]
103015828  E2F1; E2F transcription factor 1 [KO:K17454]
103017714  E2F2; E2F transcription factor 2 [KO:K09389]
103007760  E2F3; E2F transcription factor 3 [KO:K06620]
103009884  COL4A1; collagen type IV alpha 1 chain [KO:K06237]
103010470  COL4A2; collagen type IV alpha 2 chain [KO:K06237]
103009501  COL4A5; collagen type IV alpha 5 chain [KO:K06237]
103009983  COL4A6; collagen type IV alpha 6 chain [KO:K06237]
103020723  COL4A3; collagen type IV alpha 3 chain [KO:K06237]
103010606  COL4A4; collagen type IV alpha 4 chain [KO:K06237]
103011922  LAMA1; laminin subunit alpha 1 [KO:K05637]
102998029  LAMA2; laminin subunit alpha 2 [KO:K05637]
103004795  laminin subunit alpha-3-like [KO:K06240]
103010510  LAMA5; laminin subunit alpha 5 [KO:K06240]
103012309  LAMA3; laminin, alpha 3 [KO:K06240]
103014236  LAMA4; laminin subunit alpha 4 [KO:K06241]
102997450  LAMB1; laminin subunit beta 1 [KO:K05636]
102999125  LAMB2; laminin subunit beta 2 [KO:K06243]
103003030  LAMB3; laminin subunit beta 3 [KO:K06244]
103006714  LAMB4; laminin subunit beta 4 [KO:K06245]
102999353  LAMC1; laminin subunit gamma 1 [KO:K05635]
103005240  LAMC2; laminin subunit gamma 2 [KO:K06246]
103006188  LAMC3; laminin subunit gamma 3 [KO:K06247]
103018975  FN1; fibronectin 1 [KO:K05717]
103016586  ITGA2; integrin subunit alpha 2 [KO:K06481]
102999724  ITGA2B; integrin subunit alpha 2b [KO:K06476]
103017998  ITGA3; integrin subunit alpha 3 [KO:K06482]
103017654  ITGA6; integrin subunit alpha 6 [KO:K06485]
103000411  ITGAV; integrin subunit alpha V [KO:K06487]
103008019  ITGB1; integrin subunit beta 1 [KO:K05719]
103013388  PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
103012691  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103012931  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103014043  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103008077  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103009307  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103007464  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102998704  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
103002026  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103013147  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103004139  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103015414  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
103015119  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103017855  NF-kappa-B essential modulator-like [KO:K07210]
103002206  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102999230  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
103019614  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
103006934  BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
103007434  BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
103010212  XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
103008187  BIRC7; baculoviral IAP repeat containing 7 [KO:K16061]
103017903  BCL2L1; BCL2 like 1 [KO:K04570]
103010571  TRAF1; TNF receptor associated factor 1 [KO:K03172]
103013880  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
102997874  TRAF3; TNF receptor associated factor 3 [KO:K03174]
103020623  TRAF4; TNF receptor associated factor 4 [KO:K09848]
103010499  TRAF5; TNF receptor associated factor 5 [KO:K09849]
103018592  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
102999195  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
103003780  NOS2; nitric oxide synthase 2 [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
bacu04110  Cell cycle
bacu04115  p53 signaling pathway
bacu04151  PI3K-Akt signaling pathway
bacu04210  Apoptosis
bacu04510  Focal adhesion
bacu04512  ECM-receptor interaction
KO pathway
ko05222   
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