KEGG   PATHWAY: dord05222
Entry
dord05222                   Pathway                                
Name
Small cell lung cancer - Dipodomys ordii (Ord's kangaroo rat)
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
dord05222  Small cell lung cancer
dord05222

Organism
Dipodomys ordii (Ord's kangaroo rat) [GN:dord]
Gene
105981219  Fhit; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
105981337  Rarb; retinoic acid receptor beta isoform X1 [KO:K08528]
105995651  Rxra; retinoic acid receptor RXR-alpha [KO:K08524]
105999883  Rxrb; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
105989632  Rxrg; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
105983546  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
105995758  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105990235  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105988868  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
106001326  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105994373  Bax; apoptosis regulator BAX [KO:K02159]
105999887  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
105996079  Ddb2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
105992438  Polk; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
105987599  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
105991774  cytochrome c, somatic [KO:K08738]
105994518  cytochrome c, testis-specific [KO:K08738]
105987659  Apaf1; apoptotic protease-activating factor 1 [KO:K02084]
105989961  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
105992928  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
105992358  Myc; myc proto-oncogene protein [KO:K04377]
105986278  Max; protein max isoform X1 [KO:K04453]
105989956  Zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
105988954  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
105989896  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
105992920  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
105989065  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
105984811  Cks1b; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
105987402  Skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
105992216  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
105990005  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105993146  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
105982827  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
105980484  Rb1; retinoblastoma-associated protein isoform X1 [KO:K06618]
105981580  E2f1; transcription factor E2F1 [KO:K17454]
105997893  E2f2; transcription factor E2F2 [KO:K09389]
105996367  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
105990435  Col4a1; collagen alpha-1(IV) chain [KO:K06237]
105990449  Col4a2; collagen alpha-2(IV) chain [KO:K06237]
105981156  Col4a4; collagen alpha-4(IV) chain [KO:K06237]
105992792  Col4a6; collagen alpha-6(IV) chain [KO:K06237]
105992808  Col4a5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
105988294  Col4a3; collagen alpha-3(IV) chain [KO:K06237]
105993504  Lama2; laminin subunit alpha-2 [KO:K05637]
105993774  Lama1; laminin subunit alpha-1 [KO:K05637]
105984588  Lama3; laminin subunit alpha-3 [KO:K06240]
105996303  Lama5; laminin subunit alpha-5 [KO:K06240]
105998190  Lama4; laminin subunit alpha-4 [KO:K06241]
105999662  Lamb1; laminin subunit beta-1 [KO:K05636]
105994608  Lamb2; laminin subunit beta-2 [KO:K06243]
105984877  Lamb3; laminin subunit beta-3 [KO:K06244]
105999643  Lamb4; laminin subunit beta-4 [KO:K06245]
105985100  Lamc1; laminin subunit gamma-1 [KO:K05635]
105985099  Lamc2; laminin subunit gamma-2 [KO:K06246]
105989328  Lamc3; laminin subunit gamma-3 [KO:K06247]
105986628  Fn1; fibronectin [KO:K05717]
105987295  Itga2; integrin alpha-2 [KO:K06481]
105997503  Itga2b; integrin alpha-IIb [KO:K06476]
106003202  Itga3; integrin alpha-3 [KO:K06482]
105994005  Itga6; integrin alpha-6 [KO:K06485]
105995249  Itgav; integrin alpha-V [KO:K06487]
105980489  Itgb1; integrin beta-1 [KO:K05719]
105992308  Ptk2; focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
105999080  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105999614  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
106000559  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
106001473  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105985370  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105986178  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
105986227  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]
105986533  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105983045  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105998099  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105986731  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
105991714  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
106000155  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
105982592  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
105991225  Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
105989242  Rela; transcription factor p65 isoform X1 [KO:K04735]
105980764  Birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
105986903  Xiap; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
105996312  Birc7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
105981697  Bcl2l1; bcl-2-like protein 1 isoform X1 [KO:K04570]
105996183  Traf1; TNF receptor-associated factor 1 [KO:K03172]
105995582  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
105983154  Traf3; TNF receptor-associated factor 3 [KO:K03174]
105985848  Traf4; TNF receptor-associated factor 4 [KO:K09848]
105984909  Traf5; TNF receptor-associated factor 5 [KO:K09849]
105988129  Traf6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
105989626  Ptgs2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
105985658  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
dord04110  Cell cycle
dord04115  p53 signaling pathway
dord04151  PI3K-Akt signaling pathway
dord04210  Apoptosis
dord04510  Focal adhesion
dord04512  ECM-receptor interaction
KO pathway
ko05222   
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