KEGG   PATHWAY: cfr05222
Entry
cfr05222                    Pathway                                
Name
Small cell lung cancer - Camelus ferus (Wild Bactrian camel)
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
cfr05222  Small cell lung cancer
cfr05222

Organism
Camelus ferus (Wild Bactrian camel) [GN:cfr]
Gene
102522783  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
102522439  RARB; retinoic acid receptor beta isoform X2 [KO:K08528]
102518674  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
102517692  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
102517333  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
102524476  TP53; cellular tumor antigen p53 [KO:K04451]
102509404  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
102516207  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102508482  GADD45A; LOW QUALITY PROTEIN: growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
116660720  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102512073  ferritin light chain isoform X1 [KO:K02159]
102513729  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
102523860  DDB2; DNA damage-binding protein 2 isoform X4 [KO:K10140]
102507560  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
102518434  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
102524306  cytochrome c [KO:K08738]
116663281  cytochrome c-like [KO:K08738]
116663681  LOW QUALITY PROTEIN: cytochrome c, testis-specific-like [KO:K08738]
102516966  APAF1; apoptotic protease-activating factor 1 isoform X3 [KO:K02084]
102519816  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
102520133  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
102511086  MYC; myc proto-oncogene protein [KO:K04377]
102505857  MAX; protein max isoform X1 [KO:K04453]
102516215  ZBTB17; LOW QUALITY PROTEIN: zinc finger and BTB domain-containing protein 17 [KO:K10500]
116663067  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
102522300  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102520456  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
102518309  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102504059  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
102507493  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
102523584  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
102518884  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
102504649  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
102516466  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
102512815  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
102516870  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
102517851  E2F1; transcription factor E2F1 [KO:K17454]
102515523  E2F2; transcription factor E2F2 [KO:K09389]
102513737  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102524319  COL4A3; LOW QUALITY PROTEIN: collagen alpha-3(IV) chain [KO:K06237]
102524585  COL4A4; LOW QUALITY PROTEIN: collagen alpha-4(IV) chain [KO:K06237]
102509068  COL4A1; collagen alpha-1(IV) chain isoform X1 [KO:K06237]
102508830  COL4A2; LOW QUALITY PROTEIN: collagen alpha-2(IV) chain [KO:K06237]
102520494  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
102521464  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
102505642  LAMA1; laminin subunit alpha-1 isoform X1 [KO:K05637]
102504667  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
102503954  LAMA5; laminin subunit alpha-5 isoform X1 [KO:K06240]
102507092  LAMA3; LOW QUALITY PROTEIN: laminin subunit alpha-3 [KO:K06240]
102505297  LAMA4; laminin subunit alpha-4 isoform X3 [KO:K06241]
102521906  LAMB1; LOW QUALITY PROTEIN: laminin subunit beta-1 [KO:K05636]
102510254  LAMB2; laminin subunit beta-2 isoform X2 [KO:K06243]
102503746  LAMB3; LOW QUALITY PROTEIN: laminin subunit beta-3 [KO:K06244]
102521665  LAMB4; LOW QUALITY PROTEIN: laminin subunit beta-4 [KO:K06245]
102509312  LAMC1; laminin subunit gamma-1 [KO:K05635]
102509067  LAMC2; laminin subunit gamma-2 [KO:K06246]
102519796  LAMC3; laminin subunit gamma-3 isoform X1 [KO:K06247]
102518759  FN1; fibronectin isoform X1 [KO:K05717]
102522915  ITGA2; integrin alpha-2 [KO:K06481]
102521427  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
102508309  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
102518543  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
102508062  ITGAV; integrin alpha-V isoform X2 [KO:K06487]
102509512  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
102523502  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102518643  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102519994  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102513205  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
102505690  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102520923  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102515104  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]
102503460  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102515350  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102519101  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
106729149  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102503497  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102508142  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102519782  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
102519409  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102505905  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102506204  RELA; transcription factor p65 isoform X1 [KO:K04735]
102513991  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
102513751  baculoviral IAP repeat-containing protein 3 [KO:K16060]
102507842  XIAP; E3 ubiquitin-protein ligase XIAP isoform X2 [KO:K04725] [EC:2.3.2.27]
102504500  BIRC7; baculoviral IAP repeat-containing protein 7 isoform X1 [KO:K16061]
102504996  BCL2L1; bcl-2-like protein 1 isoform X2 [KO:K04570]
102511048  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
102511649  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
102515034  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
102507612  TRAF4; TNF receptor-associated factor 4 isoform X1 [KO:K09848]
102507430  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
102520181  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
102509586  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
102518523  NOS2; nitric oxide synthase, inducible isoform X1 [KO:K13241] [EC:1.14.13.39]
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
cfr04110  Cell cycle
cfr04115  p53 signaling pathway
cfr04151  PI3K-Akt signaling pathway
cfr04210  Apoptosis
cfr04510  Focal adhesion
cfr04512  ECM-receptor interaction
KO pathway
ko05222   
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