KEGG   PATHWAY: zca05222
Entry
zca05222                    Pathway                                
Name
Small cell lung cancer - Zalophus californianus (California sea lion)
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
zca05222  Small cell lung cancer
zca05222

Organism
Zalophus californianus (California sea lion) [GN:zca]
Gene
113918913  FHIT; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
113918648  RARB; retinoic acid receptor beta isoform X2 [KO:K08528]
113934741  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
113926428  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
113933383  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
113939587  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
113927327  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
113934058  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
113916383  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
113909653  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
113935677  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
113927365  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
113913864  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
113928435  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
113912489  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
113911261  cytochrome c [KO:K08738]
113926974  cytochrome c-like [KO:K08738]
113921409  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
113909591  CASP9; LOW QUALITY PROTEIN: caspase-9 [KO:K04399] [EC:3.4.22.62]
113924509  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
113911568  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
113909959  MAX; protein max isoform X1 [KO:K04453]
113928522  LOW QUALITY PROTEIN: protein max-like [KO:K04453]
113931800  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
113934560  CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685]
113921783  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
113911106  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
113914083  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
113933988  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
113933621  CKS1B; cyclin-dependent kinases regulatory subunit 1 isoform X1 [KO:K02219]
113935313  cyclin-dependent kinases regulatory subunit 2-like [KO:K02219]
113923072  cyclin-dependent kinases regulatory subunit 2-like [KO:K02219]
113935096  cyclin-dependent kinases regulatory subunit 2-like [KO:K02219]
113923570  cyclin-dependent kinases regulatory subunit 2-like [KO:K02219]
113928995  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
113922890  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
113936714  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
113930564  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
113919651  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
113938493  E2F1; transcription factor E2F1 [KO:K17454]
113912376  E2F2; transcription factor E2F2 [KO:K09389]
113927180  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
113931429  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
113931430  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
113919931  COL4A4; collagen alpha-4(IV) chain isoform X1 [KO:K06237]
113919967  COL4A3; collagen alpha-3(IV) chain isoform X1 [KO:K06237]
113920081  COL4A1; LOW QUALITY PROTEIN: collagen alpha-1(IV) chain [KO:K06237]
113920510  COL4A2; collagen alpha-2(IV) chain isoform X1 [KO:K06237]
113913157  LAMA1; laminin subunit alpha-1 [KO:K05637]
113927036  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
113912921  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
113938536  LAMA5; laminin subunit alpha-5 [KO:K06240]
113926702  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
113911882  LAMB1; laminin subunit beta-1 [KO:K05636]
113916549  LAMB2; laminin subunit beta-2 isoform X1 [KO:K06243]
113932254  LAMB3; laminin subunit beta-3 [KO:K06244]
113911883  LAMB4; laminin subunit beta-4 [KO:K06245]
113932092  LAMC1; laminin subunit gamma-1 isoform X1 [KO:K05635]
113931997  LAMC2; laminin subunit gamma-2 [KO:K06246]
113935130  LAMC3; LOW QUALITY PROTEIN: laminin subunit gamma-3 [KO:K06247]
113919318  FN1; fibronectin isoform X1 [KO:K05717]
113928431  ITGA2; integrin alpha-2 [KO:K06481]
113908302  ITGA2B; integrin alpha-IIb [KO:K06476]
113908138  ITGA3; integrin alpha-3 [KO:K06482]
113919387  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
113919409  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
113921510  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
113910123  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
113924761  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113917022  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113918898  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
113928897  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
113917179  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
113911688  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
113918785  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]
113935537  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113932035  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113910017  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113923411  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
113924180  IKBKB; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
113930597  NF-kappa-B essential modulator isoform X1 [KO:K07210]
113930605  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
118356554  NF-kappa-B essential modulator-like isoform X1 [KO:K07210]
113910226  NFKBIA; NF-kappa-B inhibitor alpha isoform X1 [KO:K04734]
113924266  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
113914948  RELA; transcription factor p65 [KO:K04735]
113914287  baculoviral IAP repeat-containing protein 2 [KO:K16060]
113914288  baculoviral IAP repeat-containing protein 3 [KO:K16060]
113930311  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
113938341  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
113936987  BCL2L1; bcl-2-like protein 1 [KO:K04570]
113934914  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
113934602  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
113908816  TRAF3; LOW QUALITY PROTEIN: TNF receptor-associated factor 3 [KO:K03174]
113939327  TRAF4; TNF receptor-associated factor 4 isoform X1 [KO:K09848]
113933278  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
113913973  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
113933515  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
113907948  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
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
zca04110  Cell cycle
zca04115  p53 signaling pathway
zca04151  PI3K-Akt signaling pathway
zca04210  Apoptosis
zca04510  Focal adhesion
zca04512  ECM-receptor interaction
KO pathway
ko05222   
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