KEGG   PATHWAY: rno05222
Entry
rno05222                    Pathway                                
Name
Small cell lung cancer - Rattus norvegicus (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
rno05222  Small cell lung cancer
rno05222

Disease
H00013  Small cell lung cancer
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
100362121  Ddb2; DNA damage-binding protein 2 [KO:K10140]
100362620  Cks2l1; cyclin-dependent kinases regulatory subunit 2-like [KO:K02219]
114483  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
114517  Itga6; integrin alpha-6 precursor [KO:K06485]
114851  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
116502  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
117036  Lamc1; laminin subunit gamma-1 precursor [KO:K05635]
120099910  [KO:K08738]
120102505  [KO:K02219]
134484121  [KO:K00922] [EC:2.7.1.153]
140433  Lama5; laminin subunit alpha-5 precursor [KO:K06240]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
170921  Itga2; integrin alpha-2 precursor [KO:K06481]
171525  Polk; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
192362  Lamc2; laminin subunit gamma-2 precursor [KO:K06246]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
24224  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
24511  Itgb1; integrin beta-1 precursor [KO:K05719]
24577  Myc; myc proto-oncogene protein [KO:K04377]
24599  Nos2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
24706  Rarb; retinoic acid receptor beta [KO:K08528]
24708  Rb1; retinoblastoma-associated protein [KO:K06618]
24842  Tp53; cellular tumor antigen p53 [KO:K04451]
24887  Bax; apoptosis regulator BAX [KO:K02159]
24888  Bcl2l1; bcl-2-like protein 1 isoform 2 [KO:K04570]
25112  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
25164  Cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25271  Rxra; retinoic acid receptor RXR-alpha [KO:K08524]
25309  Cycs; cytochrome c, somatic [KO:K08738]
25310  Cyct; cytochrome c, testis-specific [KO:K08738]
25402  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
25473  Lamb2; laminin subunit beta-2 precursor [KO:K06243]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
25614  Ptk2; focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
25661  Fn1; fibronectin precursor [KO:K05717]
25729  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
290019  Cycsl3; cytochrome c, somatic-like [KO:K08738]
290905  Col4a1; collagen alpha-1(IV) chain precursor [KO:K06237]
291005  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
291105  E2f3; transcription factor E2F3 [KO:K06620]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
294790  Skp2; S-phase kinase-associated protein 2 [KO:K03875]
29527  Ptgs2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:1.14.99.1]
296456  Itgav; integrin alpha-V isoform 1 precursor [KO:K06487]
296468  Birc7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
298941  Lamb1; laminin subunit beta-1 precursor [KO:K05636]
299626  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
303285  Traf4; TNF receptor-associated factor 4 [KO:K09848]
305078  Lamb3; laminin subunit beta-3 precursor [KO:K06244]
306628  Col4a2; collagen alpha-2(IV) chain precursor [KO:K06237]
307582  Lama3; laminin subunit alpha-3 isoform B precursor [KO:K06240]
309165  Rela; transcription factor p65 [KO:K04735]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
309368  Lama2; laminin subunit alpha-2 precursor [KO:K05637]
309816  Lama4; laminin subunit alpha-4 precursor [KO:K06241]
311245  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
311786  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
311862  Lamc3; laminin subunit gamma-3 precursor [KO:K06247]
313666  Zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
316758  Lama1; laminin subunit alpha-1 precursor [KO:K05637]
360606  Itga3; integrin alpha-3 isoform 1 [KO:K06482]
361801  Rxrb; retinoic acid receptor RXR-beta [KO:K08525]
362485  Ccne2; G1/S-specific cyclin-E2 [KO:K06626]
362788  Traf3; TNF receptor-associated factor 3 [KO:K03174]
362817  Cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
363265  Col4a3; collagen alpha-3(IV) chain precursor [KO:K06237]
363457  Col4a5; collagen alpha-5(IV) chain precursor [KO:K06237]
363458  Col4a6; collagen type IV alpha 6 chain precursor [KO:K06237]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
367149  Bax-ps1; apoptosis regulator BAX-like [KO:K02159]
399489  E2f1; transcription factor E2F1 [KO:K17454]
498709  Cks2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
499655  Cks1b; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
50557  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]
58918  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
58919  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
60371  Birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
60398  Fhit; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:3.6.1.29]
60661  Max; protein max isoform 1 [KO:K04453]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
63879  Xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
679794  Cycsl1; cytochrome c, somatic-like [KO:K08738]
681162  Cks1l; CDC28 protein kinase regulatory subunit 1-like [KO:K02219]
681314  [KO:K02159]
684111  E2f2; transcription factor E2F2 isoform X2 [KO:K09389]
684173  Traf5; TNF receptor-associated factor 5 [KO:K09849]
685269  Itga2b; integrin alpha-IIb precursor [KO:K06476]
687813  Traf1; TNF receptor-associated factor 1 [KO:K03172]
690675  Cycsl2; cytochrome c, somatic-like [KO:K08738]
78963  Apaf1; apoptotic protease-activating factor 1 [KO:K02084]
78971  Birc3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform 2 [KO:K02580]
83571  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
83574  Rxrg; retinoic acid receptor RXR-gamma [KO:K08526]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
94201  Cdk4; cyclin-dependent kinase 4 isoform 1 [KO:K02089] [EC:2.7.11.22]
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
rno04110  Cell cycle
rno04115  p53 signaling pathway
rno04151  PI3K-Akt signaling pathway
rno04210  Apoptosis
rno04510  Focal adhesion
rno04512  ECM-receptor interaction
KO pathway
ko05222   

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