KEGG   PATHWAY: mmur05222
Entry
mmur05222                   Pathway                                
Name
Small cell lung cancer - Microcebus murinus (gray mouse lemur)
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
mmur05222  Small cell lung cancer
mmur05222

Disease
H00013  Small cell lung cancer
Organism
Microcebus murinus (gray mouse lemur) [GN:mmur]
Gene
105855026  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105855091  LAMC1; laminin subunit gamma-1 [KO:K05635]
105855154  PTK2; focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
105855459  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
105855502  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105855505  PTGS2; prostaglandin G/H synthase 2 isoform X1 [KO:K11987] [EC:1.14.99.1]
105855533  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
105855571  LAMC2; laminin subunit gamma-2 [KO:K06246]
105855821  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105855966  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
105856828  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
105857697  [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
105857729  ITGB1; integrin beta-1 [KO:K05719]
105857786  ITGA2; integrin alpha-2 isoform X1 [KO:K06481]
105857888  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
105857991  NOS2; nitric oxide synthase, inducible isoform X1 [KO:K13241] [EC:1.14.13.39]
105859313  [KO:K03174]
105860510  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
105860713  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
105860899  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
105860914  LAMB1; laminin subunit beta-1 isoform X1 [KO:K05636]
105860973  LAMA3; laminin subunit alpha-3 isoform X6 [KO:K06240]
105860998  LAMA1; laminin subunit alpha-1 [KO:K05637]
105861087  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
105861093  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105861439  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105861442  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
105862660  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105862797  [KO:K06247]
105862838  COL4A3; collagen alpha-3(IV) chain isoform X1 [KO:K06237]
105862840  [KO:K06237]
105863390  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
105863408  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
105863547  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
105863738  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105864191  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
105864192  COL4A1; collagen alpha-1(IV) chain isoform X1 [KO:K06237]
105864934  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
105864946  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105865199  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105865602  BAX; apoptosis regulator BAX isoform X2 [KO:K02159]
105865706  [KO:K06247]
105865947  BCL2L1; bcl-2-like protein 1 [KO:K04570]
105866012  E2F1; transcription factor E2F1 [KO:K17454]
105867131  [KO:K04467] [EC:2.7.11.10]
105867140  [KO:K04570]
105867511  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
105867816  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
105870314  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]
105870442  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
105870453  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
105870495  [KO:K04570]
105872856  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
105873194  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
105873508  CHUK; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
105873984  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105874193  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
105874569  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
105874570  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
105874819  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105874951  LAMB2; laminin subunit beta-2 [KO:K06243]
105875121  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
105875662  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
105875715  LAMA5; laminin subunit alpha-5 isoform X1 [KO:K06240]
105875734  BIRC7; baculoviral IAP repeat-containing protein 7 isoform X1 [KO:K16061]
105875906  [KO:K08738]
105876167  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
105876174  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105876468  [KO:K08738]
105876702  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
105876728  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
105876768  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105877006  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
105877483  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105877486  TP53; cellular tumor antigen p53 [KO:K04451]
105877995  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
105878144  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
105878355  MAX; protein max isoform X1 [KO:K04453]
105878531  RELA; transcription factor p65 isoform X1 [KO:K04735]
105879310  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
105879410  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
105880516  TRAF5; LOW QUALITY PROTEIN: TNF receptor-associated factor 5 [KO:K09849]
105880564  LAMB3; laminin subunit beta-3 [KO:K06244]
105880624  [KO:K02187] [EC:3.4.22.56]
105880728  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
105880812  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
105880978  FHIT; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
105881219  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105881857  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
105882282  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
105882502  CASP3; caspase-3 isoform X2 [KO:K02187] [EC:3.4.22.56]
105882608  FN1; fibronectin isoform X1 [KO:K05717]
105882748  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
105883029  [KO:K08738]
105883183  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
105883554  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
105883940  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
105884857  DDB2; DNA damage-binding protein 2 [KO:K10140]
105885102  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
105885999  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
105886063  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
Compound
C00777  Retinoate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C15493  9-cis-Retinoic acid
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
mmur04110  Cell cycle
mmur04115  p53 signaling pathway
mmur04151  PI3K-Akt signaling pathway
mmur04210  Apoptosis
mmur04510  Focal adhesion
mmur04512  ECM-receptor interaction
KO pathway
ko05222   

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