KEGG   PATHWAY: mun05222
Entry
mun05222                    Pathway                                
Name
Small cell lung cancer - Meriones unguiculatus (Mongolian gerbil)
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
mun05222  Small cell lung cancer
mun05222

Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110565012  Fhit; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
110555070  Rarb; retinoic acid receptor beta isoform X2 [KO:K08528]
110549176  Rxra; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
110543383  Rxrb; retinoic acid receptor RXR-beta isoform X2 [KO:K08525]
110551800  Rxrg; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
110555127  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110546586  Cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
110555604  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110558423  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X2 [KO:K04402]
110559073  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110560658  Bax; apoptosis regulator BAX isoform X1 [KO:K02159]
110543676  Bak1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
110550733  Ddb2; DNA damage-binding protein 2 [KO:K10140]
110563772  Polk; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
110557800  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110545164  cytochrome c, somatic [KO:K08738]
110555979  cytochrome c, testis-specific [KO:K08738]
110563439  LOW QUALITY PROTEIN: cytochrome c, testis-specific-like [KO:K08738]
110559601  cytochrome c, somatic-like [KO:K08738]
110549868  LOW QUALITY PROTEIN: cytochrome c, somatic-like [KO:K08738]
110552819  cytochrome c, somatic-like [KO:K08738]
110541243  Apaf1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
110545060  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
132653623  Casp3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
110560064  Myc; myc proto-oncogene protein [KO:K04377]
110547767  Max; protein max isoform X1 [KO:K04453]
110544860  Zbtb17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
110554385  Cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
110561245  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
110558380  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
110546940  Ccnd1; G1/S-specific cyclin-D1 isoform X2 [KO:K04503]
110545036  Cks1b; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
110559074  Cks2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
110566051  Skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
110551008  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
110559398  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
110545702  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
110561277  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
110553592  Rb1; retinoblastoma-associated protein [KO:K06618]
110554547  E2f1; transcription factor E2F1 isoform X1 [KO:K17454]
110545385  E2f2; transcription factor E2F2 [KO:K09389]
110561800  E2f3; transcription factor E2F3 isoform X3 [KO:K06620]
110547507  Col4a4; collagen alpha-4(IV) chain [KO:K06237]
110547508  Col4a3; collagen alpha-3(IV) chain [KO:K06237]
110548883  Col4a2; collagen alpha-2(IV) chain [KO:K06237]
110548884  Col4a1; collagen alpha-1(IV) chain [KO:K06237]
110540164  Col4a5; LOW QUALITY PROTEIN: collagen alpha-5(IV) chain [KO:K06237]
110552295  Lama1; laminin subunit alpha-1 [KO:K05637]
110559223  Lama2; laminin subunit alpha-2 [KO:K05637]
110554009  Lama5; laminin subunit alpha-5 [KO:K06240]
110553478  Lama3; laminin subunit alpha-3 isoform X1 [KO:K06240]
110564967  Lama4; laminin subunit alpha-4 [KO:K06241]
110558987  Lamb1; laminin subunit beta-1 [KO:K05636]
110565216  Lamb2; laminin subunit beta-2 [KO:K06243]
110559812  Lamb3; laminin subunit beta-3 isoform X3 [KO:K06244]
110546189  Lamc1; laminin subunit gamma-1 [KO:K05635]
110546194  Lamc2; laminin subunit gamma-2 [KO:K06246]
110559252  Lamc3; laminin subunit gamma-3 isoform X1 [KO:K06247]
110557288  Fn1; fibronectin isoform X1 [KO:K05717]
110561085  Itga2; integrin alpha-2 [KO:K06481]
110551893  Itga2b; integrin alpha-IIb isoform X1 [KO:K06476]
110551197  Itga3; integrin alpha-3 isoform X2 [KO:K06482]
110563280  Itga6; integrin alpha-6 isoform X3 [KO:K06485]
110559159  Itgav; integrin alpha-V [KO:K06487]
110554841  Itgb1; integrin beta-1 isoform X2 [KO:K05719]
110542391  Ptk2; focal adhesion kinase 1 isoform X4 [KO:K05725] [EC:2.7.10.2]
110565112  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110556252  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110548394  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110553683  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110549145  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110563512  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110561175  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]
110556719  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110558966  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110564898  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110552966  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
110544653  LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
110556613  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110562528  Ikbkg; NF-kappa-B essential modulator isoform X3 [KO:K07210]
110562401  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110558602  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
110549347  Rela; transcription factor p65 isoform X1 [KO:K04735]
110553751  Birc3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
110553757  Birc2; baculoviral IAP repeat-containing protein 2 isoform X4 [KO:K16060]
110542115  Xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
110554792  Birc7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
110550083  Bcl2l1; bcl-2-like protein 1 isoform X1 [KO:K04570]
110563759  Traf1; TNF receptor-associated factor 1 isoform X3 [KO:K03172]
110557003  Traf2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
110553240  Traf3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
110544618  Traf4; TNF receptor-associated factor 4 isoform X1 [KO:K09848]
110566223  Traf5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
110557497  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
110553489  Ptgs2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
110550157  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
mun04110  Cell cycle
mun04115  p53 signaling pathway
mun04151  PI3K-Akt signaling pathway
mun04210  Apoptosis
mun04510  Focal adhesion
mun04512  ECM-receptor interaction
KO pathway
ko05222   
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