ENTRY map07233 Drug Pathway NAME Ion transporter inhibitors PATHWAY_MAP map07233 Ion transporter inhibitors COMPOUND D00112 G-Strophanthin (JAN) D00247 Bumetanide (JP18/USP/INN) D00272 Chlorthalidone (USP) D00297 Digitoxin (JAN/USP/INN) D00298 Digoxin (JP18/USP) D00313 Ethacrynic acid (USP) D00331 Furosemide (JP18/USP/INN) D00340 Hydrochlorothiazide (JP18/USP/INN) D00345 Indapamide (JP18/USP) D00355 Lansoprazole (JP18/USP/INN) D00382 Torsemide (USP) D00431 Metolazone (JAN/USP/INN) D00455 Omeprazole (JP18/USP/INN) D00461 Quinethazone (JAN/INN) D00519 Chlorothiazide (JAN/USP/INN) D00658 Trichlormethiazide (JP18/USP/INN) D00724 Rabeprazole sodium (JP18/USP) D01207 Omeprazole sodium (USAN) D01240 Deslanoside (JP18/USP/INN) D01246 Benzylhydrochlorothiazide (JAN) D01323 Azosemide (JP18/USAN/INN) D01379 Proscillaridin (JAN/USAN/INN) D01605 Meticrane (JP18/INN) D01634 Piretanide (JAN/USAN/INN) D01877 Mefruside (JP18/USAN/INN) D01895 Tripamide (JAN/USAN/INN) D01920 Tenatoprazole (JAN/INN) D01972 Lanatoside C (JAN/INN) D01984 Esomeprazole magnesium (USP) D02587 Metildigoxin (JP18) D02593 Pantoprazole sodium (USP) D04056 Esomeprazole sodium (USAN) D04079 Ethacrynate sodium (USP) D05093 Muzolimine (USAN/INN) D05259 Omeprazole magnesium (USP) D05261 Omeprazole sodium injection (JAN) D05353 Pantoprazole (USAN/INN) D06401 Indapamide hydrate D06881 Acetyldigitoxin (INN) D07147 Gitoformate (INN) D07555 Acetyldigoxin D07556 beta-Acetyldigoxin D07917 Esomeprazole (INN) D07999 Sodium furosemide D08001 Furosemide diolamine D08463 Rabeprazole (INN) D08619 Torasemide sodium D09339 Esomeprazole potassium (USAN) D09847 Metildigoxin (INN) REFERENCE AUTHORS Tanaka C., Kato R. (eds) TITLE [New pharmacology (revision 5th ed)] (In Japanese) JOURNAL Nankodo /// ENTRY map07234 Drug Pathway NAME Neurotransmitter transporter inhibitors PATHWAY_MAP map07234 Neurotransmitter transporter inhibitors COMPOUND D00110 Cocaine (USP) D00228 Amoxapine (JP18/USP/INN) D00326 Fluoxetine (USAN/INN) D00367 Mazindol (JAN/USP/INN) D00394 Trimipramine (USAN/INN) D00809 Amitriptyline hydrochloride (JP18/USP) D00811 Clomipramine hydrochloride (JP18/USP) D00812 Desipramine hydrochloride (JAN/USP) D00815 Imipramine hydrochloride (JP18/USP) D00816 Nortriptyline hydrochloride (JP18/USP/INN) D00818 Maprotiline hydrochloride (JP18/USP) D00820 Trazodone hydrochloride (JAN/USP) D00821 Venlafaxine hydrochloride (JAN/USP) D00822 Citalopram hydrobromide (USP) D00823 Fluoxetine hydrochloride (JAN/USP) D00824 Fluvoxamine maleate (JP18/USP) D00825 Sertraline hydrochloride (JAN/USP) D01107 Milnacipran hydrochloride (JAN/USAN) D01179 Duloxetine hydrochloride (JAN/USP) D01285 Lofepramine hydrochloride (JAN/USAN) D01546 Dothiepin hydrochloride (USAN) D02074 Amphetamine sulfate (USP) D02078 Dextroamphetamine sulfate (USP) D02182 Cocaine hydrochloride (JP18/USP) D02242 Methamphetamine hydrochloride (JP18/USP) D02260 Paroxetine hydrochloride hemihydrate (USP) D02360 Sertraline (INN) D02362 Paroxetine (USP/INN) D02408 Trimipramine maleate (JAN/USP) D02566 Maprotiline (USAN) D02567 Escitalopram oxalate (JAN/USP) D02570 Desvenlafaxine succinate (USAN) D02573 Reboxetine mesylate (USAN) D02574 Atomoxetine hydrochloride (JAN/USP) D02897 Amfonelic acid (USAN) D03740 Dextroamphetamine (USAN) D05173 Nisoxetine (USAN/INN) D05200 Nomifensine maleate (USAN) D05374 Paroxetine hydrochloride (USP) D05375 Paroxetine mesylate (USAN) D07334 Imipraminoxide (INN) D07445 Amfetamine (INN) D07448 Amitriptyline (INN) D07449 Amitriptylinoxide (INN) D07473 Atomoxetine (USP/INN) D07704 Citalopram (USP/INN) D07705 Citalopram hydrochloride D07727 Clomipramine (INN) D07791 Desipramine (INN) D07793 Desvenlafaxine (INN) D07872 Dosulepin (INN) D07880 Duloxetine (INN) D07913 Escitalopram (INN) D07984 Fluvoxamine (INN) D08070 Imipramine (INN) D08071 Imipramine pamoate (USP) D08140 Lofepramine (INN) D08187 Metamfetamine (INN) D08222 Milnacipran (INN) D08288 Nortriptyline (INN) D08472 Reboxetine (INN) D08626 Trazodone (INN) D08670 Venlafaxine (INN) D09340 Esreboxetine (USAN/INN) D09341 Esreboxetine succinate (USAN) REFERENCE AUTHORS Tanaka C., Kato R. (eds) TITLE [New pharmacology (revision 5th ed)] (In Japanese) JOURNAL Nankodo /// ENTRY map07235 Drug Pathway NAME N-Methyl-D-aspartic acid (NMDA) receptor antagonists PATHWAY_MAP map07235 N-Methyl-D-aspartic acid (NMDA) receptor antagonists COMPOUND C07575 Phencyclidine C13737 Dizocilpine D00711 Ketamine hydrochloride (JP18/USP) D00777 Amantadine hydrochloride (JP18/USP) D00848 Dextromethorphan hydrobromide (USP) D01445 Ifenprodil tartrate (JP18) D02102 Methadone hydrochloride (JAN/USP) D03100 Besonprodil (USAN) D03742 Dextromethorphan (USP) D03744 Dextromethorphan polistirex (USAN) D03746 Dextrorphan hydrochloride (USAN) D03878 Dizocilpine maleate (USAN) D04905 Memantine hydrochloride (JAN/USP) D05453 Phencyclidine hydrochloride (USAN) D06204 Traxoprodil mesylate (USAN) D07283 Esketamine (USAN/INN) D07441 Amantadine (INN) D08064 Ifenprodil (INN) D08098 Ketamine (INN) D08121 Levomethadone (INN) D08122 Levomethadone hydrochloride D08174 Memantine (INN) D08195 Methadone (BAN) /// ENTRY map00650 Pathway NAME Butanoate metabolism CLASS Metabolism; Carbohydrate metabolism PATHWAY_MAP map00650 Butanoate metabolism MODULE M00027 GABA (gamma-Aminobutyrate) shunt [PATH:map00650] M00088 Ketone body biosynthesis, acetyl-CoA => acetoacetate/3-hydroxybutyrate/acetone [PATH:map00650] DBLINKS GO: 0019605 REL_PATHWAY map00010 Glycolysis / Gluconeogenesis map00020 Citrate cycle (TCA cycle) map00250 Alanine, aspartate and glutamate metabolism map00330 Arginine and proline metabolism map00620 Pyruvate metabolism map00750 Vitamin B6 metabolism map01056 Biosynthesis of type II polyketide backbone KO_PATHWAY ko00650 /// ENTRY map00410 Pathway NAME beta-Alanine metabolism CLASS Metabolism; Metabolism of other amino acids PATHWAY_MAP map00410 beta-Alanine metabolism MODULE M00013 Malonate semialdehyde pathway, propanoyl-CoA => acetyl-CoA [PATH:map00410] M00046 Pyrimidine degradation, uracil => beta-alanine, thymine => 3-aminoisobutanoate [PATH:map00410] DBLINKS GO: 0019482 REL_PATHWAY map00061 Fatty acid biosynthesis map00240 Pyrimidine metabolism map00250 Alanine, aspartate and glutamate metabolism map00330 Arginine and proline metabolism map00460 Cyanoamino acid metabolism map00640 Propanoate metabolism map00770 Pantothenate and CoA biosynthesis KO_PATHWAY ko00410 /// ENTRY map05218 Pathway NAME Melanoma DESCRIPTION Melanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes. The only known environmental risk factor is exposure to ultraviolet (UV) light and in people with fair skin the risk is greatly increased. Melanoma pathogenesis is also driven by genetic factors. Oncogenic NRAS mutations activate both effector pathways Raf-MEK-ERK and PI3K-Akt. The Raf-MEK-ERK pathway may also be activated via mutations in the BRAF gene. The PI3K-Akt pathway may be activated through loss or mutation of the inhibitory tumor suppressor gene PTEN. These mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Melanoma development has been shown to be strongly associated with inactivation of the p16INK4a/cyclin dependent kinases 4 and 6/retinoblastoma protein (p16INK4a/CDK4,6/pRb) and p14ARF/human double minute 2/p53 (p14ARF/HMD2/p53) tumor suppressor pathways. MITF and TP53 are implicated in further melanoma progression. CLASS Human Diseases; Cancer: specific types PATHWAY_MAP map05218 Melanoma DISEASE H00038 Melanoma REFERENCE PMID:16822996 AUTHORS Miller AJ, Mihm MC Jr. TITLE Melanoma. JOURNAL N Engl J Med 355:51-65 (2006) DOI:10.1056/NEJMra052166 REFERENCE PMID:12894244 AUTHORS Chin L. TITLE The genetics of malignant melanoma: lessons from mouse and man. JOURNAL Nat Rev Cancer 3:559-70 (2003) DOI:10.1038/nrc1145 REFERENCE PMID:16750612 AUTHORS Takata M, Saida T. TITLE Genetic alterations in melanocytic tumors. JOURNAL J Dermatol Sci 43:1-10 (2006) DOI:10.1016/j.jdermsci.2006.05.002 REFERENCE PMID:15841168 AUTHORS Chudnovsky Y, Khavari PA, Adams AE. TITLE Melanoma genetics and the development of rational therapeutics. JOURNAL J Clin Invest 115:813-24 (2005) DOI:10.1172/JCI24808 REFERENCE PMID:16001050 AUTHORS Merlino G. TITLE Cancer biology: the weakest link? JOURNAL Nature 436:33-5 (2005) DOI:10.1038/436033a REFERENCE PMID:16001072 AUTHORS Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, Lee C, Wagner SN, Li C, Golub TR, Rimm DL, Meyerson ML, Fisher DE, Sellers WR. TITLE Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. JOURNAL Nature 436:117-22 (2005) DOI:10.1038/nature03664 REFERENCE PMID:16899407 AUTHORS Levy C, Khaled M, Fisher DE. TITLE MITF: master regulator of melanocyte development and melanoma oncogene. JOURNAL Trends Mol Med 12:406-14 (2006) DOI:10.1016/j.molmed.2006.07.008 REFERENCE PMID:15009714 AUTHORS Tsao H, Goel V, Wu H, Yang G, Haluska FG. TITLE Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma. JOURNAL J Invest Dermatol 122:337-41 (2004) DOI:10.1046/j.0022-202X.2004.22243.x REFERENCE PMID:11224709 AUTHORS Gruss C, Herlyn M. TITLE Role of cadherins and matrixins in melanoma. JOURNAL Curr Opin Oncol 13:117-23 (2001) DOI:10.1097/00001622-200103000-00006 REFERENCE PMID:15721476 AUTHORS Thompson JF, Scolyer RA, Kefford RF. TITLE Cutaneous melanoma. JOURNAL Lancet 365:687-701 (2005) DOI:10.1016/S0140-6736(05)17951-3 REFERENCE PMID:14695152 AUTHORS Omholt K, Platz A, Kanter L, Ringborg U, Hansson J. TITLE NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. JOURNAL Clin Cancer Res 9:6483-8 (2003) REFERENCE PMID:15557758 AUTHORS Hussein MR. TITLE The TP53 tumor suppressor gene and melanoma tumorigenesis: is there a relationship? JOURNAL Tumour Biol 25:200-7 (2004) DOI:10.1159/000081103 REFERENCE PMID:10843728 AUTHORS Lazar-Molnar E, Hegyesi H, Toth S, Falus A. TITLE Autocrine and paracrine regulation by cytokines and growth factors in melanoma. JOURNAL Cytokine 12:547-54 (2000) DOI:10.1006/cyto.1999.0614 REL_PATHWAY map04010 MAPK signaling pathway map04110 Cell cycle map04115 p53 signaling pathway map04151 PI3K-Akt signaling pathway map04520 Adherens junction map04916 Melanogenesis KO_PATHWAY ko05218 /// ENTRY map05219 Pathway NAME Bladder cancer DESCRIPTION The urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carcinoma are bladder carcinomas, and urothelial carcinomas of the renal pelvis and ureter account for only approximately 7% of the total. Urothelial tumours arise and evolve through divergent phenotypic pathways. Some tumours progress from urothelial hyperplasia to low-grade non-invasive superficial papillary tumours. More aggressive variants arise either from flat, high-grade carcinoma in situ (CIS) and progress to invasive tumours, or they arise de novo as invasive tumours. Low-grade papillary tumors frequently show a constitutive activation of the receptor tyrosine kinase-Ras pathway, exhibiting activating mutations in the HRAS and fibroblast growth factor receptor 3 (FGFR3) genes. In contrast, CIS and invasive tumors frequently show alterations in the TP53 and RB genes and pathways. Invasion and metastases are promoted by several factors that alter the tumour microenvironment, including the aberrant expression of E-cadherins (E-cad), matrix metalloproteinases (MMPs), angiogenic factors such as vascular endothelial growth factor (VEGF). CLASS Human Diseases; Cancer: specific types PATHWAY_MAP map05219 Bladder cancer DISEASE H00022 Bladder cancer REFERENCE PMID:17158541 AUTHORS Mitra AP, Datar RH, Cote RJ. TITLE Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification. JOURNAL J Clin Oncol 24:5552-64 (2006) DOI:10.1200/JCO.2006.08.2073 REFERENCE PMID:16474624 AUTHORS Wolff EM, Liang G, Jones PA. TITLE Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer. JOURNAL Nat Clin Pract Urol 2:502-10 (2005) DOI:10.1038/ncpuro0318 REFERENCE PMID:16110317 AUTHORS Wu XR. TITLE Urothelial tumorigenesis: a tale of divergent pathways. JOURNAL Nat Rev Cancer 5:713-25 (2005) DOI:10.1038/nrc1697 REFERENCE PMID:11103787 AUTHORS Brown NS, Jones A, Fujiyama C, Harris AL, Bicknell R. TITLE Thymidine phosphorylase induces carcinoma cell oxidative stress and promotes secretion of angiogenic factors. JOURNAL Cancer Res 60:6298-302 (2000) REFERENCE PMID:12850530 AUTHORS Bellmunt J, Hussain M, Dinney CP. TITLE Novel approaches with targeted therapies in bladder cancer. Therapy of bladder cancer by blockade of the epidermal growth factor receptor family. JOURNAL Crit Rev Oncol Hematol 46 Suppl:S85-104 (2003) DOI:10.1016/S1040-8428(03)00067-2 REFERENCE PMID:17149381 AUTHORS Sugano K, Kakizoe T. TITLE Genetic alterations in bladder cancer and their clinical applications in molecular tumor staging. JOURNAL Nat Clin Pract Urol 3:642-52 (2006) DOI:10.1038/ncpuro0649 REFERENCE PMID:15746962 AUTHORS Dunn KL, Espino PS, Drobic B, He S, Davie JR. TITLE The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling. JOURNAL Biochem Cell Biol 83:1-14 (2005) DOI:10.1139/o04-121 REFERENCE PMID:15551095 AUTHORS Williams SG, Stein JP. TITLE Molecular pathways in bladder cancer. JOURNAL Urol Res 32:373-85 (2004) DOI:10.1007/s00240-003-0345-y REL_PATHWAY map04010 MAPK signaling pathway map04012 ErbB signaling pathway map04110 Cell cycle map04115 p53 signaling pathway map04370 VEGF signaling pathway map04520 Adherens junction KO_PATHWAY ko05219 /// ENTRY map05210 Pathway NAME Colorectal cancer DESCRIPTION Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes (TSG). Two major mechanisms of genomic instability have been identified in sporadic CRC progression. The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of oncogenes such as K-ras and inactivation of TSG such as p53, DCC/Smad4, and APC. The second, known as microsatellite instability (MSI), results from inactivation of the DNA mismatch repair genes MLH1 and/or MSH2 by hypermethylation of their promoter, and secondary mutation of genes with coding microsatellites, such as transforming growth factor receptor II (TGF-RII) and BAX. Hereditary syndromes have germline mutations in specific genes (mutation in the tumour suppressor gene APC on chromosome 5q in FAP, mutated DNA mismatch repair genes in HNPCC). CLASS Human Diseases; Cancer: specific types PATHWAY_MAP map05210 Colorectal cancer DISEASE H00020 Colorectal cancer REFERENCE PMID:15000146 AUTHORS Grady WM. TITLE Genomic instability and colon cancer. JOURNAL Cancer Metastasis Rev 23:11-27 (2004) DOI:10.1023/A:1025861527711 REFERENCE PMID:16555243 AUTHORS Soreide K, Janssen EA, Soiland H, Korner H, Baak JP. TITLE Microsatellite instability in colorectal cancer. JOURNAL Br J Surg 93:395-406 (2006) DOI:10.1002/bjs.5328 REFERENCE PMID:11078609 AUTHORS Anwar S, Hall C, White J, Deakin M, Farrell W, Elder JB. TITLE Hereditary non-polyposis colorectal cancer: an updated review. JOURNAL Eur J Surg Oncol 26:635-45 (2000) DOI:10.1053/ejso.2000.0974 REFERENCE PMID:16699851 AUTHORS Takayama T, Miyanishi K, Hayashi T, Sato Y, Niitsu Y. TITLE Colorectal cancer: genetics of development and metastasis. JOURNAL J Gastroenterol 41:185-92 (2006) DOI:10.1007/s00535-006-1801-6 REFERENCE PMID:12621137 AUTHORS Lynch HT, de la Chapelle A. TITLE Hereditary colorectal cancer. JOURNAL N Engl J Med 348:919-32 (2003) DOI:10.1056/NEJMra012242 REFERENCE PMID:12951588 AUTHORS Rajagopalan H, Nowak MA, Vogelstein B, Lengauer C. TITLE The significance of unstable chromosomes in colorectal cancer. JOURNAL Nat Rev Cancer 3:695-701 (2003) DOI:10.1038/nrc1165 REFERENCE PMID:10505543 AUTHORS Behrens J. TITLE Cadherins and catenins: role in signal transduction and tumor progression. JOURNAL Cancer Metastasis Rev 18:15-30 (1999) DOI:10.1023/A:1006200102166 REFERENCE PMID:16042571 AUTHORS Behrens J. TITLE The role of the Wnt signalling pathway in colorectal tumorigenesis. JOURNAL Biochem Soc Trans 33:672-5 (2005) DOI:10.1042/BST0330672 REFERENCE PMID:15349822 AUTHORS Behrens J, Lustig B. TITLE The Wnt connection to tumorigenesis. JOURNAL Int J Dev Biol 48:477-87 (2004) DOI:10.1387/ijdb.041815jb REFERENCE PMID:9196022 AUTHORS Polakis P. TITLE The adenomatous polyposis coli (APC) tumor suppressor. JOURNAL Biochim Biophys Acta 1332:F127-47 (1997) DOI:10.1016/S0304-419X(97)00008-5 REFERENCE PMID:12737309 AUTHORS Janssen KP. TITLE Murine models of colorectal cancer: studying the role of oncogenic K-ras. JOURNAL Cell Mol Life Sci 60:495-506 (2003) DOI:10.1007/s000180300041 REFERENCE PMID:11459867 AUTHORS Adjei AA. TITLE Blocking oncogenic Ras signaling for cancer therapy. JOURNAL J Natl Cancer Inst 93:1062-74 (2001) DOI:10.1093/jnci/93.14.1062 REFERENCE PMID:15573119 AUTHORS Arakawa H. TITLE Netrin-1 and its receptors in tumorigenesis. JOURNAL Nat Rev Cancer 4:978-87 (2004) DOI:10.1038/nrc1504 REFERENCE PMID:15310786 AUTHORS Mehlen P, Fearon ER. TITLE Role of the dependence receptor DCC in colorectal cancer pathogenesis. JOURNAL J Clin Oncol 22:3420-8 (2004) DOI:10.1200/JCO.2004.02.019 REFERENCE PMID:11223406 AUTHORS Peltomaki P. TITLE DNA mismatch repair and cancer. JOURNAL Mutat Res 488:77-85 (2001) DOI:10.1016/S1383-5742(00)00058-2 REFERENCE PMID:15711891 AUTHORS Li F, Cao Y, Townsend CM Jr, Ko TC. TITLE TGF-beta signaling in colon cancer cells. JOURNAL World J Surg 29:306-11 (2005) DOI:10.1007/s00268-004-7813-6 REFERENCE PMID:11170304 AUTHORS Roman C, Saha D, Beauchamp R. TITLE TGF-beta and colorectal carcinogenesis. JOURNAL Microsc Res Tech 52:450-7 (2001) DOI:10.1002/1097-0029(20010215)52:4<450::AID-JEMT1030>3.0.CO;2-O REFERENCE PMID:16326109 AUTHORS Watson AJ. TITLE An overview of apoptosis and the prevention of colorectal cancer. JOURNAL Crit Rev Oncol Hematol 57:107-21 (2006) DOI:10.1016/j.critrevonc.2005.06.005 REFERENCE PMID:15479695 AUTHORS Watson AJ. TITLE Apoptosis and colorectal cancer. JOURNAL Gut 53:1701-9 (2004) DOI:10.1136/gut.2004.052704 REFERENCE PMID:11477132 AUTHORS Houlston RS. TITLE What we could do now: molecular pathology of colorectal cancer. JOURNAL Mol Pathol 54:206-14 (2001) DOI:10.1136/mp.54.4.206 REFERENCE PMID:19167459 AUTHORS Hector S, Prehn JH TITLE Apoptosis signaling proteins as prognostic biomarkers in colorectal cancer: a review. JOURNAL Biochim Biophys Acta 1795:117-29 (2009) DOI:10.1016/j.bbcan.2008.12.002 REFERENCE PMID:18568040 AUTHORS Karnoub AE, Weinberg RA TITLE Ras oncogenes: split personalities. JOURNAL Nat Rev Mol Cell Biol 9:517-31 (2008) DOI:10.1038/nrm2438 REFERENCE PMID:24213116 AUTHORS Wang D, Xia D, Dubois RN TITLE The Crosstalk of PTGS2 and EGF Signaling Pathways in Colorectal Cancer. JOURNAL Cancers (Basel) 3:3894-908 (2011) DOI:10.3390/cancers3043894 REFERENCE PMID:20554751 AUTHORS Dasari A, Messersmith WA TITLE New strategies in colorectal cancer: biomarkers of response to epidermal growth factor receptor monoclonal antibodies and potential therapeutic targets in phosphoinositide 3-kinase and mitogen-activated protein kinase pathways. JOURNAL Clin Cancer Res 16:3811-8 (2010) DOI:10.1158/1078-0432.CCR-09-2283 REFERENCE PMID:26149458 AUTHORS Hutchinson RA, Adams RA, McArt DG, Salto-Tellez M, Jasani B, Hamilton PW TITLE Epidermal growth factor receptor immunohistochemistry: new opportunities in metastatic colorectal cancer. JOURNAL J Transl Med 13:217 (2015) DOI:10.1186/s12967-015-0531-z REL_PATHWAY map04010 MAPK signaling pathway map04012 ErbB signaling pathway map04110 Cell cycle map04115 p53 signaling pathway map04150 mTOR signaling pathway map04151 PI3K-Akt signaling pathway map04210 Apoptosis map04310 Wnt signaling pathway map04350 TGF-beta signaling pathway KO_PATHWAY ko05210 /// ENTRY map05211 Pathway NAME Renal cell carcinoma DESCRIPTION Renal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal cancer accounts for 1-4% of cases. RCC is not a single disease, it has several morphological subtypes. Conventional RCC (clear cell RCC) accounts for ~80% of cases, followed by papillary RCC (10-15%), chromophobe RCC (5%), and collecting duct RCC (<1%). Genes potentially involved in sporadic neoplasms of each particular type are VHL, MET, BHD, and FH respectively. In the absence of VHL, hypoxia-inducible factor alpha (HIF-alpha) accumulates, leading to production of several growth factors, including vascular endothelial growth factor and platelet-derived growth factor. Activated MET mediates a number of biological effects including motility, invasion of extracellular matrix, cellular transformation, prevention of apoptosis and metastasis formation. Loss of functional FH leads to accumulation of fumarate in the cell, triggering inhibition of HPH and preventing targeted pVHL-mediated degradation of HIF-alpha. BHD mutations cause the Birt-Hogg-Dube syndrome and its associated chromophobe, hybrid oncocytic, and conventional (clear cell) RCC. CLASS Human Diseases; Cancer: specific types PATHWAY_MAP map05211 Renal cell carcinoma DISEASE H00021 Renal cell carcinoma REFERENCE PMID:16339096 AUTHORS Cohen HT, McGovern FJ. TITLE Renal-cell carcinoma. JOURNAL N Engl J Med 353:2477-90 (2005) DOI:10.1056/NEJMra043172 REFERENCE PMID:15122209 AUTHORS Pavlovich CP, Schmidt LS. TITLE Searching for the hereditary causes of renal-cell carcinoma. JOURNAL Nat Rev Cancer 4:381-93 (2004) DOI:10.1038/nrc1364 REFERENCE PMID:14634372 AUTHORS Linehan WM, Walther MM, Zbar B. TITLE The genetic basis of cancer of the kidney. JOURNAL J Urol 170:2163-72 (2003) DOI:10.1097/01.ju.0000096060.92397.ed REFERENCE PMID:15611513 AUTHORS Kim WY, Kaelin WG. TITLE Role of VHL gene mutation in human cancer. JOURNAL J Clin Oncol 22:4991-5004 (2004) DOI:10.1200/JCO.2004.05.061 REFERENCE PMID:17211469 AUTHORS Sudarshan S, Linehan WM, Neckers L. TITLE HIF and fumarate hydratase in renal cancer. JOURNAL Br J Cancer 96:403-7 (2007) DOI:10.1038/sj.bjc.6603547 REFERENCE PMID:17287871 AUTHORS Sudarshan S, Pinto PA, Neckers L, Linehan WM. TITLE Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer--a distinct form of hereditary kidney cancer. JOURNAL Nat Clin Pract Urol 4:104-10 (2007) DOI:10.1038/ncpuro0711 REFERENCE PMID:14685170 AUTHORS Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. TITLE Met, metastasis, motility and more. JOURNAL Nat Rev Mol Cell Biol 4:915-25 (2003) DOI:10.1038/nrm1261 REFERENCE PMID:18358634 AUTHORS Muller-Hocker J, Babaryka G, Schmid I, Jung A TITLE Overexpression of cyclin D1, D3, and p21 in an infantile renal carcinoma with Xp11.2 TFE3-gene fusion. JOURNAL Pathol Res Pract 204:589-97 (2008) DOI:10.1016/j.prp.2008.01.010 REFERENCE PMID:12351585 AUTHORS Bodmer D, van den Hurk W, van Groningen JJ, Eleveld MJ, Martens GJ, Weterman MA, van Kessel AG. TITLE Understanding familial and non-familial renal cell cancer. JOURNAL Hum Mol Genet 11:2489-98 (2002) DOI:10.1093/hmg/11.20.2489 REFERENCE PMID:25048860 AUTHORS Kauffman EC, Ricketts CJ, Rais-Bahrami S, Yang Y, Merino MJ, Bottaro DP, Srinivasan R, Linehan WM TITLE Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers. JOURNAL Nat Rev Urol 11:465-75 (2014) DOI:10.1038/nrurol.2014.162 REFERENCE PMID:11313942 AUTHORS Skalsky YM, Ajuh PM, Parker C, Lamond AI, Goodwin G, Cooper CS TITLE PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors. JOURNAL Oncogene 20:178-87 (2001) DOI:10.1038/sj.onc.1204056 REFERENCE PMID:19422821 AUTHORS Medendorp K, van Groningen JJ, Vreede L, Hetterschijt L, Brugmans L, van den Hurk WH, van Kessel AG TITLE The renal cell carcinoma-associated oncogenic fusion protein PRCCTFE3 provokes p21 WAF1/CIP1-mediated cell cycle delay. JOURNAL Exp Cell Res 315:2399-409 (2009) DOI:10.1016/j.yexcr.2009.04.022 REL_PATHWAY map00020 Citrate cycle (TCA cycle) map04010 MAPK signaling pathway map04066 HIF-1 signaling pathway map04120 Ubiquitin mediated proteolysis map04350 TGF-beta signaling pathway map04370 VEGF signaling pathway KO_PATHWAY ko05211 /// ENTRY C00099 Compound NAME beta-Alanine; 3-Aminopropionic acid; 3-Aminopropanoate FORMULA C3H7NO2 EXACT_MASS 89.0477 MOL_WEIGHT 89.09 REMARK Same as: D07561 REACTION R00489 R00904 R00905 R00906 R00907 R00908 R00909 R00910 R00911 R00912 R00913 R00914 R00915 R00916 R00917 R01164 R01166 R02473 R02474 R02741 R03286 R03288 R03935 R09379 R09648 R10821 PATHWAY map00240 Pyrimidine metabolism map00410 beta-Alanine metabolism map00640 Propanoate metabolism map00770 Pantothenate and CoA biosynthesis map01100 Metabolic pathways map01110 Biosynthesis of secondary metabolites map01240 Biosynthesis of cofactors map04080 Neuroactive ligand-receptor interaction map04974 Protein digestion and absorption MODULE M00046 Pyrimidine degradation, uracil => beta-alanine, thymine => 3-aminoisobutanoate M00119 Pantothenate biosynthesis, valine/L-aspartate => pantothenate M00913 Pantothenate biosynthesis, 2-oxoisovalerate/spermine => pantothenate ENZYME 1.2.1.3 1.2.1.5 1.2.1.19 1.5.1.26 2.6.1.18 2.6.1.19 2.6.1.55 2.6.1.120 2.8.3.- 3.4.13.4 3.4.13.5 3.4.13.18 3.4.13.20 3.5.1.6 3.5.1.21 3.5.1.22 3.5.1.100 3.5.3.17 4.1.1.11 4.1.1.15 6.3.2.1 6.3.2.11 6.3.2.23 6.3.2.36 6.3.2.44 BRITE Compounds with biological roles [BR:br08001] Peptides Amino acids Other amino acids C00099 beta-Alanine Amines Biogenic amines C00099 beta-Alanine DBLINKS CAS: 107-95-9 PubChem: 3399 ChEBI: 16958 KNApSAcK: C00001333 PDB-CCD: BAL NIKKAJI: J4.070C ATOM 6 1 C1b C 25.6778 -16.8919 2 C6a C 24.4732 -16.1936 3 C1b C 26.8940 -16.1936 4 O6a O 23.2571 -16.8978 5 O6a O 24.4732 -14.7912 6 N1a N 28.1045 -16.8919 BOND 5 1 1 2 1 2 1 3 1 3 2 4 1 4 2 5 2 5 3 6 1 ///