KEGG   PATHWAY: mlk05222
Entry
mlk05222                    Pathway                                
Name
Small cell lung cancer - Mustela lutreola (European mink)
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
mlk05222  Small cell lung cancer
mlk05222

Organism
Mustela lutreola (European mink) [GN:mlk]
Gene
131824080  FHIT; bis(5'-adenosyl)-triphosphatase isoform X1 [KO:K01522] [EC:3.6.1.29]
131824479  RARB; retinoic acid receptor beta isoform X1 [KO:K08528]
131813243  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
131834260  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
131815099  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
131815809  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
131833891  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
131812894  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
131823251  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
131809793  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
131817775  BAX; apoptosis regulator BAX [KO:K02159]
131834235  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
131812400  DDB2; DNA damage-binding protein 2 [KO:K10140]
131832361  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
131811845  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
131833963  cytochrome c-like [KO:K08738]
131834139  cytochrome c [KO:K08738]
131829521  cytochrome c [KO:K08738]
131839300  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
131809520  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
131820467  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
131826401  MYC; myc proto-oncogene protein [KO:K04377]
131836691  MAX; protein max isoform X1 [KO:K04453]
131809730  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
131812650  CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685]
131838541  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
131829369  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
131817001  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
131812698  CKS2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
131813098  cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
131820743  cyclin-dependent kinases regulatory subunit 2-like [KO:K02219]
131814360  CKS1B; cyclin-dependent kinases regulatory subunit 1 isoform X1 [KO:K02219]
131807527  cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
131832598  cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
131831657  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
131839026  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
131838622  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
131826589  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
131818272  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
131813843  RB1; retinoblastoma-associated protein [KO:K06618]
131807833  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
131809711  E2F2; transcription factor E2F2 [KO:K09389]
131834799  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
131827372  COL4A4; collagen alpha-4(IV) chain isoform X1 [KO:K06237]
131827373  COL4A3; collagen alpha-3(IV) chain isoform X1 [KO:K06237]
131820789  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
131813524  COL4A2; collagen alpha-2(IV) chain isoform X1 [KO:K06237]
131813526  COL4A1; collagen alpha-1(IV) chain isoform X1 [KO:K06237]
131822161  COL4A5; collagen alpha-5(IV) chain [KO:K06237]
131833812  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
131811428  LAMA1; laminin subunit alpha-1 [KO:K05637]
131811666  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
131808591  LAMA5; laminin subunit alpha-5 isoform X1 [KO:K06240]
131833489  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
131829232  LAMB1; laminin subunit beta-1 [KO:K05636]
131823907  LAMB2; laminin subunit beta-2 [KO:K06243]
131815308  LAMB3; laminin subunit beta-3 [KO:K06244]
131829234  LAMB4; laminin subunit beta-4 [KO:K06245]
131815290  LAMC1; laminin subunit gamma-1 [KO:K05635]
131814364  LAMC2; laminin subunit gamma-2 [KO:K06246]
131812737  LAMC3; laminin subunit gamma-3 isoform X1 [KO:K06247]
131827486  FN1; fibronectin isoform X1 [KO:K05717]
131831727  ITGA2; integrin alpha-2 [KO:K06481]
131816536  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
131816419  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
131827091  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
131826998  ITGAV; integrin alpha-V [KO:K06487]
131838306  ITGB1; integrin beta-1 [KO:K05719]
131826363  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
131809015  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
131824589  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
131824847  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
131823754  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
131832309  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
131810162  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
131828969  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
131828977  phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN-like isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
131828978  LOW QUALITY PROTEIN: phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN-like [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
131829020  LOW QUALITY PROTEIN: phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN-like [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
131837056  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
131815063  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
131817507  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
131828549  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
131820342  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
131822182  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
131836470  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
131829855  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
131815578  RELA; transcription factor p65 [KO:K04735]
131834540  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
131834551  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
131822235  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
131807312  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
131807889  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
131812230  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
131812685  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
131837014  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
131816559  TRAF4; TNF receptor-associated factor 4 isoform X1 [KO:K09848]
131815325  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
131811444  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
131814650  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
131816344  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
mlk04110  Cell cycle
mlk04115  p53 signaling pathway
mlk04151  PI3K-Akt signaling pathway
mlk04210  Apoptosis
mlk04510  Focal adhesion
mlk04512  ECM-receptor interaction
KO pathway
ko05222   
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