KEGG   PATHWAY: bbis05222
Entry
bbis05222                   Pathway                                
Name
Small cell lung cancer - Bison bison bison (American bison)
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
bbis05222  Small cell lung cancer
bbis05222

Organism
Bison bison bison (American bison) [GN:bbis]
Gene
104997071  FHIT; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
104993244  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
104986307  photoreceptor-specific nuclear receptor-like [KO:K08524]
104988000  hepatocyte nuclear factor 4-alpha-like [KO:K08524]
104994893  RXRB; retinoic acid receptor RXR-beta [KO:K08525]
104997302  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
104990761  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
104994949  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
104992057  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105005583  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
104996168  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
104995631  BAX; apoptosis regulator BAX [KO:K02159]
104994906  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
104990347  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
104994135  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
104999231  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
104999778  cytochrome c [KO:K08738]
104988504  cytochrome c-like [KO:K08738]
105002922  cytochrome c 2 [KO:K08738]
104982240  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
104995965  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
104985538  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
104991741  MYC; myc proto-oncogene protein [KO:K04377]
104993471  MAX; protein max isoform X1 [KO:K04453]
104996107  ZBTB17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
104998244  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
104988133  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
104988453  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
104987056  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
104992061  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
104987423  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
104998552  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
105002174  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
104988050  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
104983944  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
104996613  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
104984371  RB1; retinoblastoma-associated protein [KO:K06618]
104981106  E2F2; transcription factor E2F2 [KO:K09389]
104995083  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
104986452  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
104986509  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
104982141  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
104982142  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
105002469  LAMA1; laminin subunit alpha-1 isoform X1 [KO:K05637]
104984744  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
104980294  laminin subunit alpha-3-like [KO:K06240]
104990035  LAMA5; laminin subunit alpha-5 [KO:K06240]
105000633  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
104989710  LAMB1; laminin subunit beta-1 [KO:K05636]
104997220  laminin subunit beta-2 isoform X1 [KO:K06243]
104997293  laminin subunit beta-2-like [KO:K06243]
104986342  LAMB3; laminin subunit beta-3 [KO:K06244]
104989732  LAMB4; LOW QUALITY PROTEIN: laminin subunit beta-4 [KO:K06245]
104998110  LAMC1; laminin subunit gamma-1 [KO:K05635]
104998109  LAMC2; laminin subunit gamma-2 [KO:K06246]
105000876  LAMC3; LOW QUALITY PROTEIN: laminin subunit gamma-3 [KO:K06247]
105003740  FN1; fibronectin isoform X1 [KO:K05717]
105001056  ITGA2; integrin alpha-2 isoform X1 [KO:K06481]
104982983  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
104990610  ITGA3; LOW QUALITY PROTEIN: integrin alpha-3 [KO:K06482]
104991399  ITGA6; integrin alpha-6 [KO:K06485]
105002887  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
105002990  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
104984862  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
104999978  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105001799  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
104996058  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
104998445  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104992716  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104994333  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
104987508  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]
104986245  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
104995356  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104989637  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
105003597  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105002719  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
104993223  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
104985237  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
104994637  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
104987029  RELA; transcription factor p65 [KO:K04735]
104984863  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
104991056  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
104984445  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
104986198  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
104980990  bcl-2-like protein 1 [KO:K04570]
104989915  BCL2L1; bcl-2-like protein 1 [KO:K04570]
104994766  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
104982944  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
104996935  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
105003942  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
104984231  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
104982477  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
104998056  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
105003971  NOS2; 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
bbis04110  Cell cycle
bbis04115  p53 signaling pathway
bbis04151  PI3K-Akt signaling pathway
bbis04210  Apoptosis
bbis04510  Focal adhesion
bbis04512  ECM-receptor interaction
KO pathway
ko05222   
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