KEGG   PATHWAY: ko05222
Entry
ko05222                     Pathway                                
Name
Small cell lung cancer
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
ko05222  Small cell lung cancer
ko05222

Disease
H00013  Small cell lung cancer
Orthology
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01110  PTEN; phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.16 3.1.3.48 3.1.3.67]
K01522  FHIT; bis(5'-adenosyl)-triphosphatase [EC:3.6.1.29]
K02084  APAF1; apoptotic protease-activating factor
K02089  CDK4; cyclin-dependent kinase 4 [EC:2.7.11.22]
K02091  CDK6; cyclin-dependent kinase 6 [EC:2.7.11.22]
K02159  BAX; apoptosis regulator BAX
K02161  BCL2; apoptosis regulator Bcl-2
K02187  CASP3; caspase 3 [EC:3.4.22.56]
K02206  CDK2; cyclin-dependent kinase 2 [EC:2.7.11.22]
K02219  CKS1; cyclin-dependent kinase regulatory subunit CKS1
K02580  NFKB1; nuclear factor NF-kappa-B p105 subunit
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03172  TRAF1; TNF receptor-associated factor 1
K03173  TRAF2; TNF receptor-associated factor 2 [EC:2.3.2.27]
K03174  TRAF3; TNF receptor-associated factor 3
K03175  TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27]
K03511  POLK; DNA polymerase kappa [EC:2.7.7.7]
K03875  SKP2, FBXL1; F-box and leucine-rich repeat protein 1 (S-phase kinase-associated protein 2)
K04377  MYC; Myc proto-oncogene protein
K04399  CASP9; caspase 9 [EC:3.4.22.62]
K04402  GADD45; growth arrest and DNA-damage-inducible protein
K04451  TP53, P53; tumor protein p53
K04453  MAX; Max protein
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04467  IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K04503  CCND1; G1/S-specific cyclin-D1
K04570  BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04685  CDKN2B, P15, INK4B; cyclin-dependent kinase inhibitor 2B
K04725  XIAP, BIRC4; E3 ubiquitin-protein ligase XIAP [EC:2.3.2.27]
K04734  NFKBIA; NF-kappa-B inhibitor alpha
K04735  RELA; transcription factor p65
K05635  LAMC1; laminin, gamma 1
K05636  LAMB1; laminin, beta 1
K05637  LAMA1_2; laminin, alpha 1/2
K05717  FN1; fibronectin 1
K05719  ITGB1, CD29; integrin beta 1
K05725  PTK2, FAK; focal adhesion kinase 1 [EC:2.7.10.2]
K06237  COL4A; collagen type IV alpha
K06240  LAMA3_5; laminin, alpha 3/5
K06241  LAMA4; laminin, alpha 4
K06243  LAMB2; laminin, beta 2
K06244  LAMB3; laminin, beta 3
K06245  LAMB4; laminin, beta 4
K06246  LAMC2; laminin, gamma 2
K06247  LAMC3; laminin, gamma 3
K06476  ITGA2B, CD41; integrin alpha 2B
K06481  ITGA2, CD49b; integrin alpha 2
K06482  ITGA3, CD49c; integrin alpha 3
K06485  ITGA6, CD49f; integrin alpha 6
K06487  ITGAV, CD51; integrin alpha V
K06618  RB1; retinoblastoma-associated protein
K06620  E2F3; transcription factor E2F3
K06624  CDKN1B, P27, KIP1; cyclin-dependent kinase inhibitor 1B
K06625  CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A
K06626  CCNE; G1/S-specific cyclin-E1
K07209  IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K08524  RXRA, NR2B1; retinoid X receptor alpha
K08525  RXRB, NR2B2; retinoid X receptor beta
K08526  RXRG, NR2B3; retinoid X receptor gamma
K08528  RARB, NR1B2; retinoic acid receptor beta
K08738  CYC; cytochrome c
K09389  E2F2; transcription factor E2F2
K09848  TRAF4; TNF receptor-associated factor 4
K09849  TRAF5; TNF receptor-associated factor 5
K10140  DDB2; DNA damage-binding protein 2
K10500  ZBTB17, MIZ1; zinc finger and BTB domain-containing protein 17
K11987  PTGS2, COX2; prostaglandin-endoperoxide synthase 2 [EC:1.14.99.1]
K13241  NOS2; nitric-oxide synthase, inducible [EC:1.14.13.39]
K14021  BAK, BAK1; Bcl-2 homologous antagonist/killer
K16060  BIRC2_3; baculoviral IAP repeat-containing protein 2/3
K16061  BIRC7_8; baculoviral IAP repeat-containing protein 7/8
K17454  E2F1; transcription factor E2F1
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
ko04110  Cell cycle
ko04115  p53 signaling pathway
ko04151  PI3K-Akt signaling pathway
ko04210  Apoptosis
ko04510  Focal adhesion
ko04512  ECM-receptor interaction

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