KEGG PATHWAY: ko05222

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; Cancers

Pathway map

ko05222

Small cell lung cancer

Disease

H00013

Small cell lung cancer

Orthology

K01522	bis(5'-adenosyl)-triphosphatase [EC:3.6.1.29]
K08528	retinoic acid receptor beta
K08524	retinoid X receptor alpha
K08525	retinoid X receptor beta
K08526	retinoid X receptor gamma
K04451	tumor protein p53
K02161	apoptosis regulator BCL-2
K08738	cytochrome c
K02084	apoptotic protease-activating factor
K04399	caspase 9 [EC:3.4.22.62]
K04377	Myc proto-oncogene protein
K04453	Max protein
K16063	E3 SUMO-protein ligase PIAS2 [EC:6.3.2.-]
K04685	cyclin-dependent kinase inhibitor 2B
K02089	cyclin-dependent kinase 4 [EC:2.7.11.22]
K02091	cyclin-dependent kinase 6 [EC:2.7.11.22]
K04503	cyclin D1
K02219	cyclin-dependent kinase regulatory subunit CKS1
K03875	F-box and leucine-rich repeat protein 1 (S-phase kinase-associated protein 2)
K02206	cyclin-dependent kinase 2 [EC:2.7.11.22]
K06626	cyclin E
K06618	retinoblastoma-associated protein
K06620	E2F transcription factor 1/3
K09389	E2F transcription factor 2
K06237	collagen, type IV, alpha
K05637	laminin, alpha 1/2
K06240	laminin, alpha 3/5
K06241	laminin, alpha 4
K05636	laminin, beta 1
K06243	laminin, beta 2
K06244	laminin, beta 3
K06245	laminin, beta 4
K05635	laminin, gamma 1
K06246	laminin, gamma 2
K06247	laminin, gamma 3
K05717	fibronectin 1
K06481	integrin alpha 2
K06476	integrin alpha 2B
K06482	integrin alpha 3
K06485	integrin alpha 6
K06487	integrin alpha V
K05719	integrin beta 1
K05725	focal adhesion kinase 1 [EC:2.7.10.2]
K00922	phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153]
K02649	phosphoinositide-3-kinase, regulatory subunit
K01110	phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.67 3.1.3.48 3.1.3.16]
K04456	RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04467	inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209	inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210	inhibitor of nuclear factor kappa-B kinase subunit gamma
K04734	NF-kappa-B inhibitor alpha
K02580	nuclear factor NF-kappa-B p105 subunit
K04735	transcription factor p65
K16060	baculoviral IAP repeat-containing protein 2/3
K04725	E3 ubiquitin-protein ligase XIAP
K16061	baculoviral IAP repeat-containing protein 7/8
K04570	BCL2-like 1 (apoptosis regulator Bcl-X)
K03172	TNF receptor-associated factor 1
K03173	TNF receptor-associated factor 2
K03174	TNF receptor-associated factor 3
K09848	TNF receptor-associated factor 4
K09849	TNF receptor-associated factor 5
K03175	TNF receptor-associated factor 6
K11987	prostaglandin-endoperoxide synthase 2 [EC:1.14.99.1]
K13241	nitric-oxide synthase, inducible [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)

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)

Reference

PMID:12711111

Authors

Sanchez-Cespedes M.

Title

Dissecting the genetic alterations involved in lung carcinogenesis.

Journal

Lung Cancer 40:111-21 (2003)

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)

Reference

PMID:11720739

Authors

Kaye FJ.

Title

Molecular biology of lung cancer.

Journal

Lung Cancer 34 Suppl 2:S35-41 (2001)

Reference

PMID:16112428

Authors

Panani AD, Roussos C.

Title

Cytogenetic and molecular aspects of lung cancer.

Journal

Cancer Lett 239:1-9 (2006)

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)

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)

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)

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)

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)

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)

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)

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)

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)

All links

Ontology (1)   
   KEGG BRITE (1)   
Pathway (2)   
   KEGG PATHWAY (1)   
   BioSystems (1)   
Disease (1)   
   KEGG DISEASE (1)   
Chemical substance (3)   
   KEGG COMPOUND (3)   
Chemical reaction (13)   
   KEGG ENZYME (13)   
Gene (65)   
   KEGG ORTHOLOGY (65)   
Literature (16)   
   PubMed (16)   
All databases (101)   

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