KEGG   PATHWAY: oga05222
Entry
oga05222                    Pathway                                
Name
Small cell lung cancer - Otolemur garnettii (small-eared galago)
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
oga05222  Small cell lung cancer
oga05222

Organism
Otolemur garnettii (small-eared galago) [GN:oga]
Gene
100942960  FHIT; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
100956106  RARB; retinoic acid receptor beta [KO:K08528]
100962073  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
100962161  RXRB; retinoic acid receptor RXR-beta isoform X2 [KO:K08525]
100941535  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
100963622  TP53; cellular tumor antigen p53 [KO:K04451]
100946725  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100946928  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100950782  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100950842  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X2 [KO:K04402]
100957285  BAX; apoptosis regulator BAX [KO:K02159]
100941755  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
100962402  DDB2; DNA damage-binding protein 2 [KO:K10140]
100966233  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
100955447  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100952744  cytochrome c, somatic [KO:K08738]
100946237  cytochrome c [KO:K08738]
100961637  cytochrome c, testis-specific [KO:K08738]
100951508  cytochrome c-like [KO:K08738]
100959812  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
100957904  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
100961435  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100952981  MYC; myc proto-oncogene protein [KO:K04377]
100943049  MAX; protein max isoform X1 [KO:K04453]
100943501  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X2 [KO:K10500]
100955700  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100960589  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100952236  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100958947  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
111722450  cyclin-dependent kinases regulatory subunit 1-like [KO:K02219]
100952432  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
100966062  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
100942708  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
100964179  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100964880  CDK2; cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
100958215  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
100959381  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
100951476  RB1; retinoblastoma-associated protein [KO:K06618]
100957114  E2F1; transcription factor E2F1 [KO:K17454]
100956861  E2F2; transcription factor E2F2 [KO:K09389]
100942819  E2F3; transcription factor E2F3 [KO:K06620]
100965274  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
100945835  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
100945623  COL4A1; collagen alpha-1(IV) chain isoform X1 [KO:K06237]
100945519  COL4A6; collagen alpha-6(IV) chain [KO:K06237]
100950977  COL4A2; LOW QUALITY PROTEIN: collagen alpha-2(IV) chain [KO:K06237]
100958142  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
100964155  LAMA1; laminin subunit alpha-1 [KO:K05637]
100950964  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
100962025  LAMA3; laminin subunit alpha-3 [KO:K06240]
100954183  LAMA5; laminin subunit alpha-5 [KO:K06240]
100964189  LAMA4; laminin subunit alpha-4 [KO:K06241]
100944569  LAMB1; laminin subunit beta-1 [KO:K05636]
100952566  LAMB2; laminin subunit beta-2 [KO:K06243]
100965771  LAMB3; laminin subunit beta-3 [KO:K06244]
100947087  LAMB4; laminin subunit beta-4 [KO:K06245]
100953638  LAMC1; laminin subunit gamma-1 [KO:K05635]
100953119  LAMC2; laminin subunit gamma-2 [KO:K06246]
100960612  LAMC3; laminin subunit gamma-3 [KO:K06247]
100948167  FN1; fibronectin isoform X2 [KO:K05717]
100949511  ITGA2; integrin alpha-2 [KO:K06481]
100951652  ITGA2B; integrin alpha-IIb [KO:K06476]
100950802  ITGA3; integrin alpha-3 [KO:K06482]
100962528  ITGA6; integrin alpha-6 [KO:K06485]
100945899  ITGAV; integrin alpha-V [KO:K06487]
100955745  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
100962373  PTK2; focal adhesion kinase 1 isoform X2 [KO:K05725] [EC:2.7.10.2]
100947138  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100953367  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100954109  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100956838  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
100952580  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
100949858  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100959283  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]
100959825  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100955276  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100945977  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100949554  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100946157  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100958883  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
100947991  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100951061  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100957990  RELA; transcription factor p65 isoform X3 [KO:K04735]
100951387  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
100951719  LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 2-like [KO:K16060]
100950019  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
100951522  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100957318  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
100953032  BCL2L1; bcl-2-like protein 1 [KO:K04570]
100959720  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
100966378  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
100947925  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
100948546  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
100957799  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
100945817  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100944482  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
100958618  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
oga04110  Cell cycle
oga04115  p53 signaling pathway
oga04151  PI3K-Akt signaling pathway
oga04210  Apoptosis
oga04510  Focal adhesion
oga04512  ECM-receptor interaction
KO pathway
ko05222   
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