KEGG   PATHWAY: psiu05222
Entry
psiu05222                   Pathway                                
Name
Small cell lung cancer - Phocoena sinus (vaquita)
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
psiu05222  Small cell lung cancer
psiu05222

Organism
Phocoena sinus (vaquita) [GN:psiu]
Gene
116762496  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
116752765  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
116755213  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
116761744  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
116757744  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
116745739  TP53; cellular tumor antigen p53 [KO:K04451]
116762584  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
116756129  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
116740948  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
116752262  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
116744670  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
116762061  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
116757742  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
116750717  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
116738931  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
116752884  cytochrome c-like [KO:K08738]
116759632  cytochrome c [KO:K08738]
116762684  cytochrome c-like [KO:K08738]
116749491  cytochrome c-like [KO:K08738]
116756700  cytochrome c 2 [KO:K08738]
116752326  cytochrome c [KO:K08738]
116760585  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
116757481  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
116746660  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
116742545  MYC; myc proto-oncogene protein [KO:K04377]
116749058  MAX; protein max isoform X1 [KO:K04453]
116763264  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
116755636  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
116760381  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
116759522  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
116757387  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
116755083  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
116740585  CKS1B; cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
116752049  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
116760537  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
116760157  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
116744703  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
116742324  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
116743055  RB1; retinoblastoma-associated protein [KO:K06618]
116740076  E2F1; transcription factor E2F1 [KO:K17454]
116748863  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
116762281  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
116747864  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
116748067  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
116756400  COL4A4; collagen alpha-4(IV) chain isoform X1 [KO:K06237]
116756805  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
116743163  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
116743164  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
116763252  LAMA2; LOW QUALITY PROTEIN: laminin subunit alpha-2 [KO:K05637]
116765008  LAMA1; laminin subunit alpha-1 [KO:K05637]
116739717  LAMA5; laminin subunit alpha-5 isoform X1 [KO:K06240]
116765156  LAMA3; LOW QUALITY PROTEIN: laminin subunit alpha-3 [KO:K06240]
116763363  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
116759601  LAMB1; laminin subunit beta-1 isoform X1 [KO:K05636]
116761805  LAMB2; laminin subunit beta-2 isoform X1 [KO:K06243]
116741523  LAMB3; laminin subunit beta-3 isoform X1 [KO:K06244]
116750559  LAMC1; laminin subunit gamma-1 isoform X1 [KO:K05635]
116756094  LAMC2; laminin subunit gamma-2 isoform X1 [KO:K06246]
116756082  LAMC3; laminin subunit gamma-3 [KO:K06247]
116756945  FN1; fibronectin isoform X1 [KO:K05717]
116750842  ITGA2; integrin alpha-2 [KO:K06481]
116746301  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
116745368  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
116756709  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
116757071  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
116748884  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
116742653  PTK2; LOW QUALITY PROTEIN: focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
116752953  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116752990  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
116751286  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116750604  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116742613  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
116751944  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116741761  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]
116743673  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116759669  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116748950  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116741676  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
116746707  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
116747398  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
116749797  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
116754222  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
116758150  RELA; transcription factor p65 isoform X1 [KO:K04735]
116757989  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
116758079  BIRC2; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 2 [KO:K16060]
116747379  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
116739818  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
116739841  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
116755406  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
116755387  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
116748433  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
116745209  TRAF4; TNF receptor-associated factor 4 [KO:K09848]
116738804  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
116757663  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
116759534  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
116745263  NOS2; LOW QUALITY PROTEIN: 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
psiu04110  Cell cycle
psiu04115  p53 signaling pathway
psiu04151  PI3K-Akt signaling pathway
psiu04210  Apoptosis
psiu04510  Focal adhesion
psiu04512  ECM-receptor interaction
KO pathway
ko05222   
LinkDB

DBGET integrated database retrieval system