KEGG   PATHWAY: pbg05222
Entry
pbg05222                    Pathway                                
Name
Small cell lung cancer - Prionailurus bengalensis (leopard cat)
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
pbg05222  Small cell lung cancer
pbg05222

Organism
Prionailurus bengalensis (leopard cat) [GN:pbg]
Gene
122487383  FHIT; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
122492062  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
122475004  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
122489388  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
122476622  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
122484900  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
122489448  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
122480620  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
122486654  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
122474523  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
122494846  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
122489414  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
122484438  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
122489887  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
122470833  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
122488013  cytochrome c [KO:K08738]
122479500  cytochrome c, testis-specific-like [KO:K08738]
122491714  cytochrome c-like [KO:K08738]
122473077  cytochrome c-like [KO:K08738]
122472567  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
122479964  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
122470647  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
122495809  MYC; myc proto-oncogene protein [KO:K04377]
122469223  MAX; LOW QUALITY PROTEIN: protein max [KO:K04453]
122479975  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
122475138  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
122473830  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
122487880  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
122484101  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
122476586  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
122475459  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
122494612  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
122473385  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
122473734  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
122494162  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
122495617  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
122482016  RB1; retinoblastoma-associated protein [KO:K06618]
122496358  E2F1; transcription factor E2F1 [KO:K17454]
122480087  E2F2; transcription factor E2F2 [KO:K09389]
122489188  E2F3; transcription factor E2F3 [KO:K06620]
122481853  COL4A4; collagen alpha-4(IV) chain isoform X1 [KO:K06237]
122481854  collagen alpha-3(IV) chain-like isoform X1 [KO:K06237]
122480338  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
122479647  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
122477549  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
122477664  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
122489971  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
122470575  LAMA1; laminin subunit alpha-1 [KO:K05637]
122470645  LAMA3; LOW QUALITY PROTEIN: laminin subunit alpha-3 [KO:K06240]
122467189  LAMA5; laminin subunit alpha-5 isoform X1 [KO:K06240]
122489882  LAMA4; LOW QUALITY PROTEIN: laminin subunit alpha-4 [KO:K06241]
122487737  LAMB1; laminin subunit beta-1 [KO:K05636]
122488689  LAMB2; laminin subunit beta-2 isoform X1 [KO:K06243]
122476346  LAMB3; laminin subunit beta-3 [KO:K06244]
122487736  LAMB4; laminin subunit beta-4 [KO:K06245]
122476097  LAMC1; laminin subunit gamma-1 [KO:K05635]
122475881  LAMC2; laminin subunit gamma-2 [KO:K06246]
122475400  LAMC3; laminin subunit gamma-3 [KO:K06247]
122481737  FN1; fibronectin isoform X1 [KO:K05717]
122493943  ITGA2; integrin alpha-2 [KO:K06481]
122485686  ITGA2B; integrin alpha-IIb [KO:K06476]
122486099  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
122481459  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
122481545  ITGAV; integrin alpha-V [KO:K06487]
122473976  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
122495851  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
122482064  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122491710  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122491934  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122487093  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122480440  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
122489641  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
122493436  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]
122469592  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122494042  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122476061  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122493134  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
122472994  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
122477442  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
122469008  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
122478010  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
122484468  RELA; transcription factor p65 [KO:K04735]
122482885  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
122482886  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
122477723  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
122467169  BIRC7; baculoviral IAP repeat-containing protein 7 isoform X1 [KO:K16061]
122496407  BCL2L1; bcl-2-like protein 1 [KO:K04570]
122475453  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
122474992  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
122469573  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
122485148  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
122476367  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
122483712  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
122475760  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
122485185  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
pbg04110  Cell cycle
pbg04115  p53 signaling pathway
pbg04151  PI3K-Akt signaling pathway
pbg04210  Apoptosis
pbg04510  Focal adhesion
pbg04512  ECM-receptor interaction
KO pathway
ko05222   
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