KEGG   PATHWAY: aamp05222
Entry
aamp05222                   Pathway                                
Name
Small cell lung cancer - Arvicola amphibius (Eurasian water vole)
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
aamp05222  Small cell lung cancer
aamp05222

Organism
Arvicola amphibius (Eurasian water vole) [GN:aamp]
Gene
119828114  Fhit; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
119827403  Rarb; retinoic acid receptor beta isoform X1 [KO:K08528]
119818907  Rxra; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
119822749  Rxrb; retinoic acid receptor RXR-beta isoform X3 [KO:K08525]
119827442  Rxrg; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
119818608  cellular tumor antigen p53-like [KO:K04451]
119813419  Tp53; cellular tumor antigen p53 [KO:K04451]
119823049  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
119822349  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
119816942  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
119807493  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
119802627  Bax; apoptosis regulator BAX isoform X1 [KO:K02159]
119823918  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
119815700  Ddb2; DNA damage-binding protein 2 [KO:K10140]
119809608  Polk; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
119827718  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
119807948  cytochrome c, somatic-like [KO:K08738]
119827640  cytochrome c, somatic-like [KO:K08738]
119812378  cytochrome c, somatic [KO:K08738]
119812503  cytochrome c, somatic-like [KO:K08738]
119819008  cytochrome c, testis-specific [KO:K08738]
119807481  cytochrome c, somatic [KO:K08738]
119803346  Apaf1; apoptotic protease-activating factor 1 [KO:K02084]
119817619  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
119812861  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
119822940  Myc; myc proto-oncogene protein [KO:K04377]
119825996  protein max-like [KO:K04453]
119805389  LOW QUALITY PROTEIN: protein max-like [KO:K04453]
119820001  Max; protein max isoform X1 [KO:K04453]
119817725  Zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
119817430  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
119803317  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
119807882  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
119827335  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
119800746  Cks1b; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
119816959  Cks2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
119814276  cyclin-dependent kinases regulatory subunit 1-like [KO:K02219]
119809590  Skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
119805439  LOW QUALITY PROTEIN: S-phase kinase-associated protein 2-like [KO:K03875]
119805441  S-phase kinase-associated protein 2-like [KO:K03875]
119805442  S-phase kinase-associated protein 2-like [KO:K03875]
119807071  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
119803337  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
119820977  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
119804174  G1/S-specific cyclin-E2-like [KO:K06626]
119826163  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
119800094  Rb1; retinoblastoma-associated protein [KO:K06618]
119815142  E2f1; transcription factor E2F1 [KO:K17454]
119816691  E2f2; transcription factor E2F2 [KO:K09389]
119817711  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
119804378  Col4a6; LOW QUALITY PROTEIN: collagen alpha-6(IV) chain [KO:K06237]
119804832  Col4a5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
119812350  Col4a1; collagen alpha-1(IV) chain [KO:K06237]
119812512  Col4a2; collagen alpha-2(IV) chain [KO:K06237]
119820835  Col4a4; collagen alpha-4(IV) chain [KO:K06237]
119820836  Col4a3; LOW QUALITY PROTEIN: collagen alpha-3(IV) chain [KO:K06237]
119803917  Lama1; laminin subunit alpha-1 [KO:K05637]
119820891  Lama2; laminin subunit alpha-2 isoform X1 [KO:K05637]
119814499  Lama3; laminin subunit alpha-3 isoform X1 [KO:K06240]
119814925  Lama5; laminin subunit alpha-5 [KO:K06240]
119821243  Lama4; laminin subunit alpha-4 isoform X1 [KO:K06241]
119818873  Lamb1; laminin subunit beta-1 [KO:K05636]
119809168  Lamb2; laminin subunit beta-2 [KO:K06243]
119827216  Lamb3; laminin subunit beta-3 [KO:K06244]
119827740  Lamc1; laminin subunit gamma-1 [KO:K05635]
119827480  Lamc2; laminin subunit gamma-2 [KO:K06246]
119819149  Lamc3; laminin subunit gamma-3 [KO:K06247]
119820335  Fn1; fibronectin isoform X1 [KO:K05717]
119809195  Itga2; integrin alpha-2 [KO:K06481]
119812773  Itga2b; integrin alpha-IIb [KO:K06476]
119812125  Itga3; integrin alpha-3 [KO:K06482]
119819436  Itga6; integrin alpha-6 isoform X1 [KO:K06485]
119818595  Itgav; integrin alpha-V isoform X1 [KO:K06487]
119802025  Itgb1; integrin beta-1 [KO:K05719]
119823930  Ptk2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
119816315  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119810503  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119826317  Pik3ca; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119808979  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119817743  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
119812102  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
119806133  Pten; LOW QUALITY PROTEIN: 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]
119818643  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119820487  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119827246  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119816335  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
119812324  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
119804668  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
119818958  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
119801102  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
119803437  Rela; transcription factor p65 isoform X1 [KO:K04735]
119809564  baculoviral IAP repeat-containing protein 3 [KO:K16060]
119809632  Birc2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
119804616  E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
119814007  Birc7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
119815691  Bcl2l1; bcl-2-like protein 1 [KO:K04570]
119819361  Traf1; TNF receptor-associated factor 1 [KO:K03172]
119818726  Traf2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
119818887  Traf3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
119813293  Traf4; TNF receptor-associated factor 4 [KO:K09848]
119827796  Traf5; TNF receptor-associated factor 5 [KO:K09849]
119814858  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
119827843  Ptgs2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
119811441  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
aamp04110  Cell cycle
aamp04115  p53 signaling pathway
aamp04151  PI3K-Akt signaling pathway
aamp04210  Apoptosis
aamp04510  Focal adhesion
aamp04512  ECM-receptor interaction
KO pathway
ko05222   
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