KEGG   PATHWAY: mcal05222
mcal05222                   Pathway                                

Small cell lung cancer - Mus caroli (Ryukyu mouse)
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
mcal05222  Small cell lung cancer

Mus caroli (Ryukyu mouse) [GN:mcal]
110309527  Fhit; bis(5'-adenosyl)-triphosphatase [KO:K01522] [EC:]
110309199  Rarb; retinoic acid receptor beta isoform X1 [KO:K08528]
110308122  Rxra; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
110312146  Rxrb; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
110290588  Rxrg; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
110305297  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110283679  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
110303739  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110296344  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
110308191  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110297919  Bax; apoptosis regulator BAX isoform X1 [KO:K02159]
110283660  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
110290093  Ddb2; DNA damage-binding protein 2 [KO:K10140]
110308520  Polk; DNA polymerase kappa isoform X1 [KO:K03511] [EC:]
110302433  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110303728  cytochrome c, somatic-like [KO:K08738]
110309371  cytochrome c, testis-specific [KO:K08738]
110296815  cytochrome c, somatic [KO:K08738]
110302801  Apaf1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
110293440  Casp9; caspase-9 [KO:K04399] [EC:]
110299851  Casp3; caspase-3 [KO:K02187] [EC:]
110310583  Myc; myc proto-oncogene protein [KO:K04377]
110306748  Max; protein max isoform X1 [KO:K04453]
110292743  Zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
110292822  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
110303132  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:]
110294345  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:]
110298189  Ccnd1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
110290541  cyclin-dependent kinases regulatory subunit 1 [KO:K02219]
110308238  Cks2; cyclin-dependent kinases regulatory subunit 2 [KO:K02219]
110300971  cyclin-dependent kinases regulatory subunit 2-like [KO:K02219]
110310405  Skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
110296846  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
110303221  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:]
110292124  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
110298604  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
110309179  Rb1; retinoblastoma-associated protein [KO:K06618]
110289983  E2f1; transcription factor E2F1 isoform X1 [KO:K17454]
110293508  E2f2; transcription factor E2F2 [KO:K09389]
110308034  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
110286404  collagen alpha-6(IV) chain-like [KO:K06237]
110299671  Col4a1; collagen alpha-1(IV) chain [KO:K06237]
110299672  Col4a2; collagen alpha-2(IV) chain [KO:K06237]
110289599  Col4a3; collagen alpha-3(IV) chain [KO:K06237]
110295504  Col4a4; collagen alpha-4(IV) chain [KO:K06237]
110286219  Col4a5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
110302840  Lama2; laminin subunit alpha-2 [KO:K05637]
110312520  Lama1; laminin subunit alpha-1 [KO:K05637]
110285111  Lama3; laminin subunit alpha-3 [KO:K06240]
110302955  Lama4; laminin subunit alpha-4 isoform X1 [KO:K06241]
110306938  Lamb1; laminin subunit beta-1 isoform X1 [KO:K05636]
110301253  Lamb2; laminin subunit beta-2 [KO:K06243]
110305044  Lamb3; laminin subunit beta-3 isoform X1 [KO:K06244]
110311961  Lamc1; laminin subunit gamma-1 isoform X1 [KO:K05635]
110300039  Lamc2; laminin subunit gamma-2 [KO:K06246]
110312505  Lamc3; laminin subunit gamma-3 [KO:K06247]
110283623  Fn1; fibronectin isoform X1 [KO:K05717]
110308074  Itga2; integrin alpha-2 [KO:K06481]
110304761  Itga2b; integrin alpha-IIb [KO:K06476]
110304308  Itga3; integrin alpha-3 isoform X1 [KO:K06482]
110285509  Itga6; integrin alpha-6 [KO:K06485]
110311058  Itgav; integrin alpha-V isoform X1 [KO:K06487]
110299930  Itgb1; integrin beta-1 [KO:K05719]
110310271  Ptk2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:]
110290798  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
110292183  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:]
110301355  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:]
110308009  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110299855  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
110292624  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110285202  Pten; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:]
110297609  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
110294471  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:]
110307022  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
110285285  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:]
110300158  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:]
110287188  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
110306864  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110291231  Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
110285703  Rela; transcription factor p65 [KO:K04735]
110302303  baculoviral IAP repeat-containing protein 3 [KO:K16060]
110301861  Birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
110286671  Xiap; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:]
110290468  Birc7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
110288823  Bcl2l1; bcl-2-like protein 1 [KO:K04570]
110289943  Traf1; TNF receptor-associated factor 1 [KO:K03172]
110289986  Traf2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:]
110306954  Traf3; TNF receptor-associated factor 3 [KO:K03174]
110305822  Traf4; TNF receptor-associated factor 4 [KO:K09848]
110296886  Traf5; TNF receptor-associated factor 5 [KO:K09849]
110290132  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:]
110292340  prostaglandin G/H synthase 2 [KO:K11987] [EC:]
110288090  LOW QUALITY PROTEIN: prostaglandin G/H synthase 2-like [KO:K11987] [EC:]
110288092  prostaglandin G/H synthase 2-like [KO:K11987] [EC:]
110288093  prostaglandin G/H synthase 2-like [KO:K11987] [EC:]
110304621  Nos2; nitric oxide synthase, inducible isoform X1 [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)
mcal04110  Cell cycle
mcal04115  p53 signaling pathway
mcal04151  PI3K-Akt signaling pathway
mcal04210  Apoptosis
mcal04510  Focal adhesion
mcal04512  ECM-receptor interaction
KO pathway

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