BCAT1促进肿瘤发生发展的研究进展
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摘要
支链氨基酸转移酶1(branched-chain amino acid transaminase 1,BCAT1)是催化支链氨基酸代谢的关键酶.国内外研究已证实BCAT1在多种恶性肿瘤中呈现高表达,并提示与肿瘤细胞增殖、转移及侵袭密切相关.本文拟就BCAT1的理化性质、生物学功能及其与肿瘤发生、发展的相关研究进行简要综述,为进一步研究BCAT1与恶性肿瘤的关系提供线索.
Branched chain amino transaminase 1(BCAT1)is a key enzyme that catalyzes the metabolism of branched chain amino acid. Research has proven that BCAT1 is highly expressed in a variety of malignant tumors, and closely related to tumor cell proliferation, metastasis and invasion. In this article, we will review the physical and chemical properties and biological functions of BCAT1 as well as its role in tumor occurrence and development.
Branched chain amino transaminase 1(BCAT1)is a key enzyme that catalyzes the metabolism of branched chain amino acid. Research has proven that BCAT1 is highly expressed in a variety of malignant tumors, and closely related to tumor cell proliferation, metastasis and invasion. In this article, we will review the physical and chemical properties and biological functions of BCAT1 as well as its role in tumor occurrence and development.
引文
1 Chen W,Zheng R,Baade PD,Zhang S,Zeng H,Bray F,Jemal A,Yu XQ,He J.Cancer statistics in China,2015.CA Cancer J Clin 2016;66:115-132[PMID:26808342 DOI:10.3322/caac.21338]
2 Eden A,Benvenisty N.Involvement of branchedchain amino acid aminotransferase(Bcat1/Eca39)in apoptosis.FEBS Lett 1999;457:255-261[PMID:10471790 DOI:10.1016/S0014-5793(99)01054-6]
3 Bonnefoy M,Laville M,Ecochard R,Jusot JF,Normand S,Maillot S,Lebreton B,Jauffret M.Effects of branched amino acids supplementation in malnourished elderly with catabolic status.J Nutr Health Aging 2010;14:579-584[PMID:20818474 DOI:10.1007/s12603-010-0090-1]
4 Wang L,Liu R,Lin F,Lin F,Liu J,Xia Z.Research Progress in Effect of Branched-chain Amino Acids on Exercise.Amino Acids&Biotic Resources 2015;1
5 Tom A,Nair KS.Assessment of branched-chain amino Acid status and potential for biomarkers.JNutr 2006;136:324S-330S[PMID:16365107]
6 Niwa O,Kumazaki T,Tsukiyama T,Soma G,Miyajima N,Yokoro K.A cDNA clone overexpressed and amplified in a mouse teratocarcinoma line.Nucleic Acids Res 1990;18:6709[PMID:2251142DOI:10.1093/nar/18.22.6709]
7 Hull J,Hindy ME,Kehoe PG,Chalmers K,Love S,Conway ME.Distribution of the branched chain aminotransferase proteins in the human brain and their role in glutamate regulation.JNeurochem 2012;123:997-1009[PMID:23043456DOI:10.1111/jnc.12044]
8 Mayers JR,Vander Heiden MG.BCAT1 defines gliomas by IDH status.Nat Med 2013;19:816-817[PMID:23836221 DOI:10.1038/nm.3263]
9 Chen CX,Zhang HH.The Progress of BCAA in Sports Field.Tangshan Shifan Xueyuan Xuebao2014;36:81-84
10 Schuldiner O,Eden A,Ben-Yosef T,Yanuka O,Simchen G,Benvenisty N.ECA39,a conserved gene regulated by c-Myc in mice,is involved in G1/S cell cycle regulation in yeast.Proc Natl Acad Sci USA 1996;93:7143-7148[PMID:8692959 DOI:10.1073/pnas.93.14.7143]
11 Eden A,Simchen G,Benvenisty N.Two yeast homologs of ECA39,a target for c-Myc regulation,code for cytosolic and mitochondrial branched-chain amino acid aminotransferases.JBiol Chem 1996;271:20242-20245[PMID:8702755DOI:10.1074/jbc.271.34.20242]
12 Ben-Yosef T,Eden A,Benvenisty N.Characterization of murine BCAT genes:Bcat1,a c-Myc target,and its homolog,Bcat2.Mamm Genome 1998;9:595-597[PMID:9657861 DOI:10.1007/s003359900825]
13 Viguerie N,Montastier E,Maoret JJ,Roussel B,Combes M,Valle C,Villa-Vialaneix N,Iacovoni JS,Martinez JA,Holst C,Astrup A,Vidal H,Clément K,Hager J,Saris WH,Langin D.Determinants of human adipose tissue gene expression:impact of diet,sex,metabolic status,and cis genetic regulation.PLoS Genet 2012;8:e1002959[PMID:23028366 DOI:10.1371/journal.pgen.1002959]
14 Grimm CH,Rogner UC,Avner P.Lrmp and Bcat1 are candidates for the type I diabetes susceptibility locus Idd6.Autoimmunity 2003;36:241-246[PMID:14563018 DOI:10.1080/0891693031000141068]
15 Greco D,Kotronen A,Westerbacka J,Puig O,Arkkila P,Kiviluoto T,Laitinen S,Kolak M,Fisher RM,Hamsten A,Auvinen P,Yki-Jvinen H.Gene expression in human NAFLD.Am J Physiol Gastrointest Liver Physiol 2008;294:G1281-G1287[PMID:18388185 DOI:10.1152/ajpgi.00074.2008]
16 Mardinoglu A,Agren R,Kampf C,Asplund A,Uhlen M,Nielsen J.Genome-scale metabolic modelling of hepatocytes reveals serine defi ciency in patients with non-alcoholic fatty liver disease.Nat Commun 2014;5:3083[PMID:24419221 DOI:10.1038/ncomms4083]
17 Kingwell K.Alzheimer disease:CSF levels of mitochondrial DNA-a new biomarker for preclinical Alzheimer disease?Nat Rev Neurol2013;9:420[PMID:23835537 DOI:10.1038/nrneurol.2013.134]
18 Hull J,Patel V,El Hindy M,Lee C,Odeleye E,Hezwani M,Love S,Kehoe P,Chalmers K,Conway M.Regional Increase in the Expression of the BCAT Proteins in Alzheimer’s Disease Brain:Implications in Glutamate Toxicity.JAlzheimers Dis 2015;45:891-905[PMID:25633671DOI:10.3233/JAD-142970]
19 Pereboom TC,Bondt A,Pallaki P,Klasson TD,Goos YJ,Essers PB,Groot Koerkamp MJ,Gazda HT,Holstege FC,Costa LD,MacInnes AW.Translation of branched-chain aminotransferase-1transcripts is impaired in cells haploinsufficient for ribosomal protein genes.Exp Hematol 2014;42:394-403.e4[PMID:24463277 DOI:10.1016/j.exphem.2013.12.010]
20 Gupta K,Salunke P.Molecular markers of glioma:an update on recent progress and perspectives.JCancer Res Clin Oncol 2012;138:1971-1981[PMID:23052697 DOI:10.1007/s00432-012-1323-y]
21 T?njes M,Barbus S,Park YJ,Wang W,Schlotter M,Lindroth AM,Pleier SV,Bai AH,Karra D,Piro RM,Felsberg J,Addington A,Lemke D,Weibrecht I,Hovestadt V,Rolli CG,Campos B,Turcan S,Sturm D,Witt H,Chan TA,HeroldMende C,Kemkemer R,K?nig R,Schmidt K,Hull WE,Pfister SM,Jugold M,Hutson SM,Plass C,Okun JG,Reifenberger G,Lichter P,Radlwimmer B.BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wildtype IDH1.Nat Med 2013;19:901-908[PMID:23793099 DOI:10.1038/nm.3217]
22 Radlwimmer B,T?njes M,Barbus S,Lichter P.Inhibitors of branched-chain-aminotransferase-1(bcat1)for the treatment of brain tumors.wo,us20130310545 a1[p].2013
23张国滨,张晋,徐恒周,周益强,程森,刘福生.支链氨基酸氨基转移酶1在恶性胶质瘤中的表达及意义.中华神经外科杂志2015;31:1259-1262
24 Kamran SC,Riaz N,Lee N.Nasopharyngeal carcinoma.Surg Oncol Clin N Am 2015;24:547-561[PMID:25979399 DOI:10.1016/j.soc.2015.03.008]
25黄仲曦.生物信息学初步探索鼻咽癌发病机理.广州:第一军医大学,2003
26 Zhou W,Feng X,Li H,Wang L,Li H,Zhu B,Zhang H,Yao K,Ren C.Functional evidence for a nasopharyngeal carcinoma-related gene BCAT1located at 12p12.Oncol Res 2007;16:405-413[PMID:18074675]
27 Zhou W,Feng X,Ren C,Jiang X,Liu W,Huang W,Liu Z,Li Z,Zeng L,Wang L,Zhu B,Shi J,Liu J,Zhang C,Liu Y,Yao K.Over-expression of BCAT1,a c-Myc target gene,induces cell proliferation,migration and invasion in nasopharyngeal carcinoma.Mol Cancer 2013;12:53[PMID:23758864 DOI:10.1186/1476-4598-12-53]
28 Bertuccio P,Turati F,Carioli G,Rodriguez T,La Vecchia C,Malvezzi M,Negri E.Global Trends and Predictions in Hepatocellular Carcinoma Mortality.J Hepatol 2017 Mar 20[Epub ahead of print][PMID:28336466 DOI:10.1016/j.jhep.2017.03.011]
29 Wei KR,Peng XB,Liang ZH.Liver Cancer Epidemiology Worldwide.China Cancer 2015;8[DOI:10.11735/j.issn.1004-0242.2015.08.A001]
30 Borzio M,Fornari F,De Sio I,Andriulli A,Terracciano F,Parisi G,Francica G,Salvagnini M,Marignani M,Salmi A,Farinati F,Carella A,Pedicino C,Dionigi E,Fanigliulo L,Cazzaniga M,Ginanni B,Sacco R.Adherence to American Association for the Study of Liver Diseases guidelines for the management of hepatocellular carcinoma:results of an Italian field practice multicenter study.Future Oncol 2013;9:283-294[PMID:23414477 DOI:10.2217/fon.12.183]
31 Wang HG,Xie R,Shen P,Huang XD,Ji GZ,Yang XZ.BCAT1 expression in hepatocellular carcinoma.Clin Res Hepatol Gastroenterol 2016;40:e55-e56[PMID:27137984 DOI:10.1016/j.clinre.2016.03.003]
32 Xu M,Liu Q,Jia Y,Tu K,Yao Y,Liu Q,Guo C.BCAT1 promotes tumor cell migration and invasion in hepatocellular carcinoma.Oncol Lett 2016;12:2648-2656[PMID:27698837 DOI:10.3892/ol.2016.4969]
33 Zheng YH,Hu WJ,Chen BC,Grahn TH,Zhao YR,Bao HL,Zhu YF,Zhang QY.BCAT1,a key prognostic predictor of hepatocellular carcinoma,promotes cell proliferation and induces chemoresistance to cisplatin.Liver Int 2016;36:1836-1847[PMID:27246112 DOI:10.1111/liv.13178]
34 Siegel RL,Miller KD,Fedewa SA,Ahnen DJ,Meester RG,Barzi A,Jemal A.Colorectal cancer statistics,2017.CA Cancer J Clin 2017 Mar 1[Epub ahead of print][PMID:28248415 DOI:10.3322/caac.21395]
35 Zhu J,Tan Z,Hollis-Hansen K,Zhang Y,Yu C,Li Y.Epidemiological Trends in Colorectal Cancer in China:An Ecological Study.Dig Dis Sci 2017;62:235-243[PMID:27796769 DOI:10.1007/s10620-016-4362-4]
36 Yoshikawa R,Yanagi H,Shen CS,Fujiwara Y,Noda M,Yagyu T,Gega M,Oshima T,Yamamura T,Okamura H,Nakano Y,Morinaga T,Hashimoto-Tamaoki T.ECA39 is a novel distant metastasis-related biomarker in colorectal cancer.World J Gastroenterol 2006;12:5884-5889[PMID:17007058 DOI:10.3748/wjg.v12.i36.5884]
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2 Eden A,Benvenisty N.Involvement of branchedchain amino acid aminotransferase(Bcat1/Eca39)in apoptosis.FEBS Lett 1999;457:255-261[PMID:10471790 DOI:10.1016/S0014-5793(99)01054-6]
3 Bonnefoy M,Laville M,Ecochard R,Jusot JF,Normand S,Maillot S,Lebreton B,Jauffret M.Effects of branched amino acids supplementation in malnourished elderly with catabolic status.J Nutr Health Aging 2010;14:579-584[PMID:20818474 DOI:10.1007/s12603-010-0090-1]
4 Wang L,Liu R,Lin F,Lin F,Liu J,Xia Z.Research Progress in Effect of Branched-chain Amino Acids on Exercise.Amino Acids&Biotic Resources 2015;1
5 Tom A,Nair KS.Assessment of branched-chain amino Acid status and potential for biomarkers.JNutr 2006;136:324S-330S[PMID:16365107]
6 Niwa O,Kumazaki T,Tsukiyama T,Soma G,Miyajima N,Yokoro K.A cDNA clone overexpressed and amplified in a mouse teratocarcinoma line.Nucleic Acids Res 1990;18:6709[PMID:2251142DOI:10.1093/nar/18.22.6709]
7 Hull J,Hindy ME,Kehoe PG,Chalmers K,Love S,Conway ME.Distribution of the branched chain aminotransferase proteins in the human brain and their role in glutamate regulation.JNeurochem 2012;123:997-1009[PMID:23043456DOI:10.1111/jnc.12044]
8 Mayers JR,Vander Heiden MG.BCAT1 defines gliomas by IDH status.Nat Med 2013;19:816-817[PMID:23836221 DOI:10.1038/nm.3263]
9 Chen CX,Zhang HH.The Progress of BCAA in Sports Field.Tangshan Shifan Xueyuan Xuebao2014;36:81-84
10 Schuldiner O,Eden A,Ben-Yosef T,Yanuka O,Simchen G,Benvenisty N.ECA39,a conserved gene regulated by c-Myc in mice,is involved in G1/S cell cycle regulation in yeast.Proc Natl Acad Sci USA 1996;93:7143-7148[PMID:8692959 DOI:10.1073/pnas.93.14.7143]
11 Eden A,Simchen G,Benvenisty N.Two yeast homologs of ECA39,a target for c-Myc regulation,code for cytosolic and mitochondrial branched-chain amino acid aminotransferases.JBiol Chem 1996;271:20242-20245[PMID:8702755DOI:10.1074/jbc.271.34.20242]
12 Ben-Yosef T,Eden A,Benvenisty N.Characterization of murine BCAT genes:Bcat1,a c-Myc target,and its homolog,Bcat2.Mamm Genome 1998;9:595-597[PMID:9657861 DOI:10.1007/s003359900825]
13 Viguerie N,Montastier E,Maoret JJ,Roussel B,Combes M,Valle C,Villa-Vialaneix N,Iacovoni JS,Martinez JA,Holst C,Astrup A,Vidal H,Clément K,Hager J,Saris WH,Langin D.Determinants of human adipose tissue gene expression:impact of diet,sex,metabolic status,and cis genetic regulation.PLoS Genet 2012;8:e1002959[PMID:23028366 DOI:10.1371/journal.pgen.1002959]
14 Grimm CH,Rogner UC,Avner P.Lrmp and Bcat1 are candidates for the type I diabetes susceptibility locus Idd6.Autoimmunity 2003;36:241-246[PMID:14563018 DOI:10.1080/0891693031000141068]
15 Greco D,Kotronen A,Westerbacka J,Puig O,Arkkila P,Kiviluoto T,Laitinen S,Kolak M,Fisher RM,Hamsten A,Auvinen P,Yki-Jvinen H.Gene expression in human NAFLD.Am J Physiol Gastrointest Liver Physiol 2008;294:G1281-G1287[PMID:18388185 DOI:10.1152/ajpgi.00074.2008]
16 Mardinoglu A,Agren R,Kampf C,Asplund A,Uhlen M,Nielsen J.Genome-scale metabolic modelling of hepatocytes reveals serine defi ciency in patients with non-alcoholic fatty liver disease.Nat Commun 2014;5:3083[PMID:24419221 DOI:10.1038/ncomms4083]
17 Kingwell K.Alzheimer disease:CSF levels of mitochondrial DNA-a new biomarker for preclinical Alzheimer disease?Nat Rev Neurol2013;9:420[PMID:23835537 DOI:10.1038/nrneurol.2013.134]
18 Hull J,Patel V,El Hindy M,Lee C,Odeleye E,Hezwani M,Love S,Kehoe P,Chalmers K,Conway M.Regional Increase in the Expression of the BCAT Proteins in Alzheimer’s Disease Brain:Implications in Glutamate Toxicity.JAlzheimers Dis 2015;45:891-905[PMID:25633671DOI:10.3233/JAD-142970]
19 Pereboom TC,Bondt A,Pallaki P,Klasson TD,Goos YJ,Essers PB,Groot Koerkamp MJ,Gazda HT,Holstege FC,Costa LD,MacInnes AW.Translation of branched-chain aminotransferase-1transcripts is impaired in cells haploinsufficient for ribosomal protein genes.Exp Hematol 2014;42:394-403.e4[PMID:24463277 DOI:10.1016/j.exphem.2013.12.010]
20 Gupta K,Salunke P.Molecular markers of glioma:an update on recent progress and perspectives.JCancer Res Clin Oncol 2012;138:1971-1981[PMID:23052697 DOI:10.1007/s00432-012-1323-y]
21 T?njes M,Barbus S,Park YJ,Wang W,Schlotter M,Lindroth AM,Pleier SV,Bai AH,Karra D,Piro RM,Felsberg J,Addington A,Lemke D,Weibrecht I,Hovestadt V,Rolli CG,Campos B,Turcan S,Sturm D,Witt H,Chan TA,HeroldMende C,Kemkemer R,K?nig R,Schmidt K,Hull WE,Pfister SM,Jugold M,Hutson SM,Plass C,Okun JG,Reifenberger G,Lichter P,Radlwimmer B.BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wildtype IDH1.Nat Med 2013;19:901-908[PMID:23793099 DOI:10.1038/nm.3217]
22 Radlwimmer B,T?njes M,Barbus S,Lichter P.Inhibitors of branched-chain-aminotransferase-1(bcat1)for the treatment of brain tumors.wo,us20130310545 a1[p].2013
23张国滨,张晋,徐恒周,周益强,程森,刘福生.支链氨基酸氨基转移酶1在恶性胶质瘤中的表达及意义.中华神经外科杂志2015;31:1259-1262
24 Kamran SC,Riaz N,Lee N.Nasopharyngeal carcinoma.Surg Oncol Clin N Am 2015;24:547-561[PMID:25979399 DOI:10.1016/j.soc.2015.03.008]
25黄仲曦.生物信息学初步探索鼻咽癌发病机理.广州:第一军医大学,2003
26 Zhou W,Feng X,Li H,Wang L,Li H,Zhu B,Zhang H,Yao K,Ren C.Functional evidence for a nasopharyngeal carcinoma-related gene BCAT1located at 12p12.Oncol Res 2007;16:405-413[PMID:18074675]
27 Zhou W,Feng X,Ren C,Jiang X,Liu W,Huang W,Liu Z,Li Z,Zeng L,Wang L,Zhu B,Shi J,Liu J,Zhang C,Liu Y,Yao K.Over-expression of BCAT1,a c-Myc target gene,induces cell proliferation,migration and invasion in nasopharyngeal carcinoma.Mol Cancer 2013;12:53[PMID:23758864 DOI:10.1186/1476-4598-12-53]
28 Bertuccio P,Turati F,Carioli G,Rodriguez T,La Vecchia C,Malvezzi M,Negri E.Global Trends and Predictions in Hepatocellular Carcinoma Mortality.J Hepatol 2017 Mar 20[Epub ahead of print][PMID:28336466 DOI:10.1016/j.jhep.2017.03.011]
29 Wei KR,Peng XB,Liang ZH.Liver Cancer Epidemiology Worldwide.China Cancer 2015;8[DOI:10.11735/j.issn.1004-0242.2015.08.A001]
30 Borzio M,Fornari F,De Sio I,Andriulli A,Terracciano F,Parisi G,Francica G,Salvagnini M,Marignani M,Salmi A,Farinati F,Carella A,Pedicino C,Dionigi E,Fanigliulo L,Cazzaniga M,Ginanni B,Sacco R.Adherence to American Association for the Study of Liver Diseases guidelines for the management of hepatocellular carcinoma:results of an Italian field practice multicenter study.Future Oncol 2013;9:283-294[PMID:23414477 DOI:10.2217/fon.12.183]
31 Wang HG,Xie R,Shen P,Huang XD,Ji GZ,Yang XZ.BCAT1 expression in hepatocellular carcinoma.Clin Res Hepatol Gastroenterol 2016;40:e55-e56[PMID:27137984 DOI:10.1016/j.clinre.2016.03.003]
32 Xu M,Liu Q,Jia Y,Tu K,Yao Y,Liu Q,Guo C.BCAT1 promotes tumor cell migration and invasion in hepatocellular carcinoma.Oncol Lett 2016;12:2648-2656[PMID:27698837 DOI:10.3892/ol.2016.4969]
33 Zheng YH,Hu WJ,Chen BC,Grahn TH,Zhao YR,Bao HL,Zhu YF,Zhang QY.BCAT1,a key prognostic predictor of hepatocellular carcinoma,promotes cell proliferation and induces chemoresistance to cisplatin.Liver Int 2016;36:1836-1847[PMID:27246112 DOI:10.1111/liv.13178]
34 Siegel RL,Miller KD,Fedewa SA,Ahnen DJ,Meester RG,Barzi A,Jemal A.Colorectal cancer statistics,2017.CA Cancer J Clin 2017 Mar 1[Epub ahead of print][PMID:28248415 DOI:10.3322/caac.21395]
35 Zhu J,Tan Z,Hollis-Hansen K,Zhang Y,Yu C,Li Y.Epidemiological Trends in Colorectal Cancer in China:An Ecological Study.Dig Dis Sci 2017;62:235-243[PMID:27796769 DOI:10.1007/s10620-016-4362-4]
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