KEGG   PATHWAY: hsa05222Help
Entry
hsa05222                    Pathway                                

Name
Small cell lung cancer - Homo sapiens (human)
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; Cancers
BRITE hierarchy
Pathway map
Small cell lung cancer
hsa05222

All organismsOrtholog table
Disease
H00013  
Small cell lung cancer
Organism
Homo sapiens (human) [GN:hsa]
Gene
2272  
FHIT; fragile histidine triad [KO:K01522] [EC:3.6.1.29]
5915  
RARB; retinoic acid receptor beta [KO:K08528]
6256  
RXRA; retinoid X receptor alpha [KO:K08524]
6257  
RXRB; retinoid X receptor beta [KO:K08525]
6258  
RXRG; retinoid X receptor gamma [KO:K08526]
7157  
TP53; tumor protein p53 [KO:K04451]
596  
BCL2; BCL2, apoptosis regulator [KO:K02161]
54205  
CYCS; cytochrome c, somatic [KO:K08738]
317  
APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
842  
CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
4609  
MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
4149  
MAX; MYC associated factor X [KO:K04453]
9063  
PIAS2; protein inhibitor of activated STAT 2 [KO:K16063]
1030  
CDKN2B; cyclin dependent kinase inhibitor 2B [KO:K04685]
1019  
CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
1021  
CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
595  
CCND1; cyclin D1 [KO:K04503]
1163  
CKS1B; CDC28 protein kinase regulatory subunit 1B [KO:K02219]
1164  
CKS2; CDC28 protein kinase regulatory subunit 2 [KO:K02219]
6502  
SKP2; S-phase kinase-associated protein 2, E3 ubiquitin protein ligase [KO:K03875]
1017  
CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
898  
CCNE1; cyclin E1 [KO:K06626]
9134  
CCNE2; cyclin E2 [KO:K06626]
5925  
RB1; RB transcriptional corepressor 1 [KO:K06618]
1869  
E2F1; E2F transcription factor 1 [KO:K17454]
1870  
E2F2; E2F transcription factor 2 [KO:K09389]
1871  
E2F3; E2F transcription factor 3 [KO:K06620]
1284  
COL4A2; collagen type IV alpha 2 [KO:K06237]
1286  
COL4A4; collagen type IV alpha 4 chain [KO:K06237]
1288  
COL4A6; collagen type IV alpha 6 chain [KO:K06237]
1282  
COL4A1; collagen type IV alpha 1 chain [KO:K06237]
1287  
COL4A5; collagen type IV alpha 5 chain [KO:K06237]
1285  
COL4A3; collagen type IV alpha 3 chain [KO:K06237]
284217  
LAMA1; laminin subunit alpha 1 [KO:K05637]
3908  
LAMA2; laminin subunit alpha 2 [KO:K05637]
3909  
LAMA3; laminin subunit alpha 3 [KO:K06240]
3911  
LAMA5; laminin subunit alpha 5 [KO:K06240]
3910  
LAMA4; laminin subunit alpha 4 [KO:K06241]
3912  
LAMB1; laminin subunit beta 1 [KO:K05636]
3913  
LAMB2; laminin subunit beta 2 [KO:K06243]
3914  
LAMB3; laminin subunit beta 3 [KO:K06244]
22798  
LAMB4; laminin subunit beta 4 [KO:K06245]
3915  
LAMC1; laminin subunit gamma 1 [KO:K05635]
3918  
LAMC2; laminin subunit gamma 2 [KO:K06246]
10319  
LAMC3; laminin subunit gamma 3 [KO:K06247]
2335  
FN1; fibronectin 1 [KO:K05717]
3673  
ITGA2; integrin subunit alpha 2 [KO:K06481]
3674  
ITGA2B; integrin subunit alpha 2b [KO:K06476]
3675  
ITGA3; integrin subunit alpha 3 [KO:K06482]
3655  
ITGA6; integrin subunit alpha 6 [KO:K06485]
3685  
ITGAV; integrin subunit alpha V [KO:K06487]
3688  
ITGB1; integrin subunit beta 1 [KO:K05719]
5747  
PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295  
PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
5728  
PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.67 3.1.3.48 3.1.3.16]
207  
AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
1147  
CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551  
IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
8517  
IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
4792  
NFKBIA; NFKB inhibitor alpha [KO:K04734]
4790  
NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  
RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
329  
BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
330  
BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
331  
XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
79444  
BIRC7; baculoviral IAP repeat containing 7 [KO:K16061]
112401  
BIRC8; baculoviral IAP repeat containing 8 [KO:K16061]
598  
BCL2L1; BCL2 like 1 [KO:K04570]
7185  
TRAF1; TNF receptor associated factor 1 [KO:K03172]
7186  
TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
7187  
TRAF3; TNF receptor associated factor 3 [KO:K03174]
9618  
TRAF4; TNF receptor associated factor 4 [KO:K09848]
7188  
TRAF5; TNF receptor associated factor 5 [KO:K09849]
7189  
TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
5743  
PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
4843  
NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]
1027  
CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
Compound
C00777  
Retinoate
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
C15493  
9-cis-Retinoic acid
Reference
  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)
Reference
  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)
Reference
  Authors
Sanchez-Cespedes M.
  Title
Dissecting the genetic alterations involved in lung carcinogenesis.
  Journal
Lung Cancer 40:111-21 (2003)
Reference
  Authors
Mitsuuchi Y, Testa JR.
  Title
Cytogenetics and molecular genetics of lung cancer.
  Journal
Am J Med Genet 115:183-8 (2002)
Reference
  Authors
Kaye FJ.
  Title
Molecular biology of lung cancer.
  Journal
Lung Cancer 34 Suppl 2:S35-41 (2001)
Reference
  Authors
Panani AD, Roussos C.
  Title
Cytogenetic and molecular aspects of lung cancer.
  Journal
Cancer Lett 239:1-9 (2006)
Reference
  Authors
Altucci L, Gronemeyer H.
  Title
The promise of retinoids to fight against cancer.
  Journal
Nat Rev Cancer 1:181-93 (2001)
Reference
  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)
Reference
  Authors
Shivapurkar N, Reddy J, Chaudhary PM, Gazdar AF.
  Title
Apoptosis and lung cancer: a review.
  Journal
J Cell Biochem 88:885-98 (2003)
Reference
  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)
Reference
  Authors
Adhikary S, Eilers M.
  Title
Transcriptional regulation and transformation by Myc proteins.
  Journal
Nat Rev Mol Cell Biol 6:635-45 (2005)
Reference
  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)
Reference
  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)
Reference
  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
  Authors
Rintoul RC, Sethi T.
  Title
The role of extracellular matrix in small-cell lung cancer.
  Journal
Lancet Oncol 2:437-42 (2001)
Reference
  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)
KO pathway
 

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