KEGG   PATHWAY: rbb05222
rbb05222                    Pathway                                

Small cell lung cancer - Rhinopithecus bieti (black snub-nosed monkey)
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.
Human Diseases; Cancer: specific types
Pathway map
rbb05222  Small cell lung cancer

Rhinopithecus bieti (black snub-nosed monkey) [GN:rbb]
108543621  FHIT; fragile histidine triad [KO:K01522] [EC:]
108543072  RARB; retinoic acid receptor beta [KO:K08528]
108513168  RXRA; retinoid X receptor alpha [KO:K08524]
108540287  RXRB; retinoid X receptor beta [KO:K08525]
108538378  RXRG; retinoid X receptor gamma [KO:K08526]
108514363  TP53; tumor protein p53 [KO:K04451]
108528336  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
108538612  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
108532870  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
108531451  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
108523624  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
108516259  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
108521962  DDB2; damage specific DNA binding protein 2 [KO:K10140]
108513078  POLK; DNA polymerase kappa [KO:K03511] [EC:]
108526412  BCL2; BCL2, apoptosis regulator [KO:K02161]
108530087  cytochrome c-like [KO:K08738]
108532915  cytochrome c [KO:K08738]
108535521  cytochrome c [KO:K08738]
108524009  cytochrome c [KO:K08738]
108538827  cytochrome c-like [KO:K08738]
108536287  cytochrome c-like [KO:K08738]
108524923  cytochrome c-like [KO:K08738]
108523439  cytochrome c-like [KO:K08738]
108533297  cytochrome c-like [KO:K08738]
108543462  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
108524269  CASP9; caspase 9 [KO:K04399] [EC:]
108512689  caspase-3-like [KO:K02187] [EC:]
108528761  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
108542424  MAX; MYC associated factor X [KO:K04453]
108524262  ZBTB17; zinc finger and BTB domain containing 17 [KO:K10500]
108537064  CDKN2B; cyclin dependent kinase inhibitor 2B [KO:K04685]
108524397  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:]
108528490  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:]
108538745  CCND1; cyclin D1 [KO:K04503]
108532236  CKS2; CDC28 protein kinase regulatory subunit 2 [KO:K02219]
108526816  CKS1B; CDC28 protein kinase regulatory subunit 1B [KO:K02219]
108529671  cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
108535053  SKP2; S-phase kinase associated protein 2 [KO:K03875]
108530341  CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
108516053  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:]
108539896  CCNE2; cyclin E2 [KO:K06626]
108530611  CCNE1; cyclin E1 [KO:K06626]
108530701  RB1; RB transcriptional corepressor 1 [KO:K06618]
108533038  E2F1; E2F transcription factor 1 [KO:K17454]
108538448  E2F2; E2F transcription factor 2 [KO:K09389]
108522131  E2F3; E2F transcription factor 3 [KO:K06620]
108527057  COL4A1; collagen type IV alpha 1 chain [KO:K06237]
108527058  COL4A2; collagen type IV alpha 2 chain [KO:K06237]
108522717  collagen alpha-6(IV) chain-like [KO:K06237]
108538728  COL4A3; collagen type IV alpha 3 chain [KO:K06237]
108538749  COL4A4; collagen type IV alpha 4 chain [KO:K06237]
108534366  LAMA2; laminin subunit alpha 2 [KO:K05637]
108523928  LAMA1; laminin subunit alpha 1 [KO:K05637]
108535245  LAMA5; laminin subunit alpha 5 [KO:K06240]
108536899  LAMA3; laminin subunit alpha 3 [KO:K06240]
108512065  LAMA4; laminin subunit alpha 4 [KO:K06241]
108540465  LAMB1; laminin subunit beta 1 [KO:K05636]
108527002  LAMB2; laminin subunit beta 2 [KO:K06243]
108539549  LAMB3; laminin subunit beta 3 [KO:K06244]
108540493  laminin subunit beta-4 [KO:K06245]
108512695  LAMC1; laminin subunit gamma 1 [KO:K05635]
108512736  LAMC2; laminin subunit gamma 2 [KO:K06246]
108513926  LAMC3; laminin subunit gamma 3 [KO:K06247]
108543178  FN1; fibronectin 1 [KO:K05717]
108522903  ITGA2; integrin subunit alpha 2 [KO:K06481]
108532191  ITGA2B; integrin subunit alpha 2b [KO:K06476]
108516444  ITGA3; integrin subunit alpha 3 [KO:K06482]
108522273  ITGA6; integrin subunit alpha 6 [KO:K06485]
108535417  ITGAV; integrin subunit alpha V [KO:K06487]
108529400  ITGB1; integrin subunit beta 1 [KO:K05719]
108544148  PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:]
108544591  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:]
108532960  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:]
108539355  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
108535636  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
108534276  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
108541175  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
108527540  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:]
108512498  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:]
108539069  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:]
108521880  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:]
108535077  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:]
108540719  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:]
108518784  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
108519636  NFKBIA; NFKB inhibitor alpha [KO:K04734]
108532817  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
108543519  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
108514076  BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
108514077  BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
108535289  BIRC7; baculoviral IAP repeat containing 7 [KO:K16061]
108524131  BCL2L1; BCL2 like 1 [KO:K04570]
108537107  TRAF1; TNF receptor associated factor 1 [KO:K03172]
108542901  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:]
108514953  TRAF3; TNF receptor associated factor 3 [KO:K03174]
108530161  TNF receptor-associated factor 4-like [KO:K09848]
108539936  TRAF4; TNF receptor associated factor 4 [KO:K09848]
108515877  TRAF5; TNF receptor associated factor 5 [KO:K09849]
108535559  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:]
108523178  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:]
108539959  NOS2; nitric oxide synthase 2 [KO:K13241] [EC:]
C00777  Retinoate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C15493  9-cis-Retinoic acid
Osada H, Takahashi T.
Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer.
Oncogene 21:7421-34 (2002)
Yokota J, Nishioka M, Tani M, Kohno T.
Genetic alterations responsible for metastatic phenotypes of lung cancer cells.
Clin Exp Metastasis 20:189-93 (2003)
Sanchez-Cespedes M.
Dissecting the genetic alterations involved in lung carcinogenesis.
Lung Cancer 40:111-21 (2003)
Mitsuuchi Y, Testa JR.
Cytogenetics and molecular genetics of lung cancer.
Am J Med Genet 115:183-8 (2002)
Kaye FJ.
Molecular biology of lung cancer.
Lung Cancer 34 Suppl 2:S35-41 (2001)
Panani AD, Roussos C.
Cytogenetic and molecular aspects of lung cancer.
Cancer Lett 239:1-9 (2006)
Altucci L, Gronemeyer H.
The promise of retinoids to fight against cancer.
Nat Rev Cancer 1:181-93 (2001)
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.
Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas.
J Natl Cancer Inst 92:1303-7 (2000)
Sartorius UA, Krammer PH.
Upregulation of Bcl-2 is involved in the mediation of chemotherapy resistance in human small cell lung cancer cell lines.
Int J Cancer 97:584-92 (2002)
Adhikary S, Eilers M.
Transcriptional regulation and transformation by Myc proteins.
Nat Rev Mol Cell Biol 6:635-45 (2005)
Spruck C, Strohmaier H, Watson M, Smith AP, Ryan A, Krek TW, Reed SI.
A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1.
Mol Cell 7:639-50 (2001)
Buttery RC, Rintoul RC, Sethi T.
Small cell lung cancer: the importance of the extracellular matrix.
Int J Biochem Cell Biol 36:1154-60 (2004)
Yamada KM, Araki M.
Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis.
J Cell Sci 114:2375-82 (2001)
Rintoul RC, Sethi T.
The role of extracellular matrix in small-cell lung cancer.
Lancet Oncol 2:437-42 (2001)
Ekedahl J, Joseph B, Grigoriev MY, Muller M, Magnusson C, Lewensohn R, Zhivotovsky B.
Expression of inhibitor of apoptosis proteins in small- and non-small-cell lung carcinoma cells.
Exp Cell Res 279:277-90 (2002)
Shivapurkar N, Reddy J, Chaudhary PM, Gazdar AF.
Apoptosis and lung cancer: a review.
J Cell Biochem 88:885-98 (2003)
Weyhenmeyer B, Murphy AC, Prehn JH, Murphy BM
Targeting the anti-apoptotic Bcl-2 family members for the treatment of cancer.
Exp Oncol 34:192-9 (2012)
rbb04110  Cell cycle
rbb04115  p53 signaling pathway
rbb04151  PI3K-Akt signaling pathway
rbb04210  Apoptosis
rbb04510  Focal adhesion
rbb04512  ECM-receptor interaction
KO pathway

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