支链氨基酸转移酶1与恶性肿瘤

doi:10.3760/cma.j.issn.1673-422X.2019.01.008

摘要/Abstract

摘要： 支链氨基酸转移酶1(BCAT1)作为催化支链氨基酸代谢的关键酶，参与多种生物合成的通路。研究发现BCAT1在白血病、胶质瘤、鼻咽癌、胃癌、乳腺癌等恶性肿瘤中高表达，与肿瘤细胞的增殖、侵袭及转移密切相关，在肿瘤的发生发展中扮演重要角色，可作为恶性肿瘤新的治疗靶点。

关键词: 肿瘤, 支链氨基酸转移酶1, 支链氨基酸

Abstract: As a key enzyme that catalyzes the metabolism of branched chain amino acids, branched chain amino acid transferase 1 (BCAT1) is often involved in a variety of biosynthetic pathways. Reaserches show that BCAT1 is highly expressed in many kinds of malignant tumors such as leukemia, glioma, nasopharyngeal carcinoma, gastric cancer and breast cancer, et al, suggesting a close relationship with the proliferation, invasion and metastasis of tumor cells. Thus, BCAT1 plays an important role in the genesis and progression of tumor, and may have the potential to be a new therapeutic target.

吕天鑫,张兵雷,宋永平. 支链氨基酸转移酶1与恶性肿瘤[J]. 国际肿瘤学杂志, 2019, 46(1): 36-39.

Lyu Tianxin, Zhang Binglei, Song Yongping. Branched chain amino acid transferase 1 and malignant tumors[J]. Journal of International Oncology, 2019, 46(1): 36-39.

参考文献

［1］ Papathanassiu AE, Ko JH, Imprialou M, et al. BCAT1 controls metabolic reprogramming in activated human macrophages and is associated with inflammatory diseases［J］. Nat Commun, 2017, 8: 16040. DOI: 10.1038/ncomms16040. ［2］赖爱军, 谢斌辉. BCAT1促进肿瘤发生发展的研究进展［J］. 世界华人消化杂志, 2017, 25(17): 1536-1542. DOI: 10.11569/wcjd.v25.i17.1536. ［3］钟巧玉, 陈懿建. 成人急性髓系白血病靶向治疗的研究进展［J］. 临床合理用药杂志, 2018, 11(25): 175-178. DOI: 10.15887/j. cnki.131389/r.2018.25.100. ［4］ Ananieva EA, Wilkinson AC. Branchedchain amino acid metabolism in cancer［J］. Curr Opin Clin Nutr Metab Care, 2018, 21(1): 64-70. DOI: 10.1097/MCO.0000000000000430. ［5］ Raffel S, Falcone M, Kneisel N, et al. BCAT1 restricts αKG levels in AML stem cells leading to IDHmutlike DNA hypermethylation［J］. Nature, 2017, 551(7680): 384-388. DOI: 10.1038/nature24294. ［6］ Kaelin WG Jr, McKnight SL. Influence of metabolism on epigenetics and disease［J］. Cell, 2013, 153(1): 5669. DOI: 10.1016/j.cell.2013.03.004. ［7］ Wang P, Wu J, Ma S, et al. Oncometabolite D2hydroxyglutarate inhibits ALKBH DNA repair enzymes and sensitizes IDH mutant cells to alkylating agents［J］. Cell Rep, 2015, 13(11): 2353-2361. DOI: 10.1016/j.celrep.2015.11.029. ［8］ Marcucci G, Maharry K, Wu YZ, et al. IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study［J］. J Clin Oncol, 2010, 28(14): 2348-2355. DOI: 10.1200/JCO.2009.27.3730. ［9］ Cancer Genome Atlas Research Network, Ley TJ, Miller C, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia［J］. N Engl J Med, 2013, 368(22): 2059-2074. DOI: 10.1056/NEJMoa1301689. ［10］ Ng SW, Mitchell A, Kennedy JA, et al. A 17gene stemness score for rapid determination of risk in acute leukaemia［J］. Nature, 2016, 540(7633): 433-437. DOI: 10.1038/nature20598. ［11］ Hattori A, Tsunoda M, Konuma T, et al. Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia［J］. Nature, 2017, 545(7655): 500-504. DOI: 10.1038/nature22314. ［12］中华医学会血液学分会. 中国慢性髓性白血病诊断与治疗指南(2013年版)［J］. 中华血液学杂志, 2013, 34(5): 464-470. DOI: 10.3760/cma.j.issn.0253-2727.2013.05.021. ［13］ Sutherland JM, McLaughlin EA, Hime GR, et al. The Musashi family of RNA binding proteins: master regulators of multiple stem cell populations［J］. Adv Exp Med Biol, 2013, 786: 233-245. DOI: 10.1007/978-94-007-6621-1_13. ［14］ Rentas S, Holzapfel N, Belew MS, et al. Musashi2 attenuates AHR signalling to expand human haematopoietic stem cells［J］. Nature, 2016, 532(7600): 508-511. DOI: 10.1038/nature17665. ［15］阙丽萍, 黄科. 儿童急性淋巴细胞白血病复发机制的研究进展［J］. 中国小儿血液与肿瘤杂志, 2016, 21(6): 322-326. DOI: 10.3969/j.issn.1673-5323.2016.06.010. ［16］李琴, 李晓明, 邢宏运. 成人急性淋巴细胞白血病发病机制研究进展［J］. 临床合理用药杂志, 2017, 10(22): 177-178. DOI: 10.15887/j.cnki.13-1389/r.2017.22.105. ［17］ Safavi S, Hansson M, Karlsson K, et al. Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia［J］. Haematologica, 2015, 100(1): 55-61. DOI: 10.3324/haematol.2014.112912. ［18］ Tnjes M, Barbus S, Park YJ, et al. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wildtype IDH1［J］. Nat Med, 2013, 19(7): 901-908. DOI: 10.1038/nm. 3217. ［19］ Zhou W, Feng X, Li H, et al. Functional evidence for a nasopharyngeal carcinomarelated gene BCAT1 located at 12pl2［J］. Oncol Res, 2007, 16(9): 405413. ［20］ Zhou W, Feng X, Ren C, et al. Overexpression of BCAT1, a cMyc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma［J］. Mol Cancer, 2013, 12: 53. DOI: 10.1186/147645981253. ［21］ Xu Y, Yu W, Yang T, et al. Overexpression of BCAT1 is a prognostic marker in gastric cancer［J］. Hum Pathol, 2018, 75: 41-46. DOI: 10.1016/j.humpath.2018.02.003. ［22］ Thewes V, Simon R, Hlevnjak M, et al. The branchedchain amino acid transaminase 1 sustains growth of antiestrogenresistant and ERαnegative breast cancer［J］. Oncogene, 2017, 36(29): 4124-4134. DOI: 10.1038/onc.2017.32. ［23］ Zhang L, Han J. Branchedchain amino acid transaminase 1 (BCAT1) promotes the growth of breast cancer cells through improving mTORmediated mitochondrial biogenesis and function［J］. Biochem Biophys Res Commun, 2017, 486(2): 224-231. DOI: 10.1016/j.bbrc.2017.02.101. ［24］ Oktyabri D, Ishimura A, Tange S, et al. DOT1L histone methyltransferase regulates the expression of BCAT1 and is involved in sphere formation and cell migration of breast cancer cell lines［J］. Biochimie, 2016, 123: 20-31. DOI: 10.1016/j.biochi.2016.01.005. ［25］ Wang ZQ, Faddaoui A, Bachvarova M, et al. BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism［J］. Oncotarget, 2015, 6(31): 31522-31543. DOI: 10.18632/oncotarget.5159. ［26］ Mayers JR, Torrence ME, Danai LV, et al. Tissue of origin dictates branchedchain amino acid metabolism in mutant Krasdriven cancers［J］. Science, 2016, 353(6304): 1161-1165. DOI: 10.1126/science.aaf5171.

[1]	刘娜, 寇介丽, 杨枫, 刘桃桃, 李丹萍, 韩君蕊, 杨立洲. 血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值[J]. 国际肿瘤学杂志, 2024, 51(6): 321-325.
[2]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊. 局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[3]	袁健, 黄燕华. Hp-IgG抗体联合血清DKK1、sB7-H3对早期胃癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(6): 338-343.
[4]	陈红健, 张素青. 血清miR-24-3p、H2AFX与肝癌患者临床病理特征及术后复发的关系研究[J]. 国际肿瘤学杂志, 2024, 51(6): 344-349.
[5]	郭泽浩, 张俊旺. PFDN及其亚基在肿瘤发生发展中的作用[J]. 国际肿瘤学杂志, 2024, 51(6): 350-353.
[6]	张百红, 岳红云. 新作用机制的抗肿瘤药物进展[J]. 国际肿瘤学杂志, 2024, 51(6): 354-358.
[7]	许凤琳, 吴刚. EBV在鼻咽癌肿瘤免疫微环境和免疫治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 359-363.
[8]	王盈, 刘楠, 郭兵. 抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[9]	张蕊, 褚衍六. 基于FIT与肠道菌群的结直肠癌风险评估模型的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 370-375.
[10]	高凡, 王萍, 杜超, 褚衍六. 肠道菌群与结直肠癌非手术治疗的相关研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 376-381.
[11]	王丽, 刘志华, 杨伟洪, 蒋凤莲, 李全泳, 宋浩杰, 鞠文东. ROS1突变肺腺鳞癌合并脑梗死为主要表现的Trousseau综合征1例[J]. 国际肿瘤学杂志, 2024, 51(6): 382-384.
[12]	刘静, 刘芹, 黄梅. 基于SMOTE算法的食管癌放化疗患者肺部感染的预后模型构建[J]. 国际肿瘤学杂志, 2024, 51(5): 267-273.
[13]	杨琳, 路宁, 温华, 张明鑫, 朱琳. 炎症负荷指数与胃癌临床关系研究[J]. 国际肿瘤学杂志, 2024, 51(5): 274-279.
[14]	王俊毅, 洪楷彬, 纪荣佳, 陈大朝. 癌结节对结直肠癌根治性切除术后肝转移的影响[J]. 国际肿瘤学杂志, 2024, 51(5): 280-285.
[15]	张宁宁, 杨哲, 檀丽梅, 李振宁, 王迪, 魏永志. 宫颈细胞DNA倍体分析联合B7-H4和PKCδ对宫颈癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(5): 286-291.