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癌症中的支链氨基酸代谢。

Branched-chain amino acid metabolism in cancer.

机构信息

aDepartment of Biochemistry and Nutrition, Des Moines University, Des Moines, IowabDepartment of Genetics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lorry I. Lokey Stem Cell Research Building, Stanford, California, USA.

出版信息

Curr Opin Clin Nutr Metab Care. 2018 Jan;21(1):64-70. doi: 10.1097/MCO.0000000000000430.

Abstract

PURPOSE OF REVIEW

The current review aims to provide an update on the recent biomedical interest in oncogenic branched-chain amino acid (BCAA) metabolism, and discusses the advantages of using BCAAs and expression of BCAA-related enzymes in the treatment and diagnosis of cancers.

RECENT FINDINGS

An accumulating body of evidence demonstrates that BCAAs are essential nutrients for cancer growth and are used by tumors in various biosynthetic pathways and as a source of energy. In addition, BCAA metabolic enzymes, such as the cytosolic branched-chain aminotransferase 1 (BCAT1) and mitochondrial branched-chain aminotransferase 2, have emerged as useful prognostic cancer markers. BCAT1 expression commonly correlates with more aggressive cancer growth and progression, and has attracted substantial scientific attention in the past few years. These studies have found the consequences of BCAT1 disruption to be heterogeneous; not all cancers share the same requirements for BCAA metabolites and the function of BCAT1 appears to vary between cancer types.

SUMMARY

Both oncogenic mutations and cancer tissue-of-origin influence BCAA metabolism and expression of BCAA-associated metabolic enzymes. These new discoveries need to be taken into consideration during the development of new cancer therapies that target BCAA metabolism.

摘要

目的综述

本篇综述旨在介绍致癌支链氨基酸(BCAA)代谢的近期生物医学研究进展,并讨论了在癌症治疗和诊断中使用 BCAA 及表达 BCAA 相关酶的优势。

最近的发现

越来越多的证据表明,BCAA 是肿瘤生长所必需的营养物质,并被肿瘤用于各种生物合成途径和作为能量来源。此外,BCAA 代谢酶,如胞质支链氨基酸转氨酶 1(BCAT1)和线粒体支链氨基酸转氨酶 2,已成为有前途的预后肿瘤标志物。BCAT1 的表达通常与更具侵袭性的癌症生长和进展相关,并在过去几年中引起了广泛的科学关注。这些研究发现,BCAT1 破坏的后果是多种多样的;并非所有癌症都具有相同的 BCAA 代谢物需求,并且 BCAT1 的功能似乎在不同的癌症类型之间有所不同。

总结

致癌突变和癌症组织起源都会影响 BCAA 代谢和 BCAA 相关代谢酶的表达。在开发靶向 BCAA 代谢的新癌症治疗方法时,需要考虑这些新发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e58/5732628/38fe0882dbb9/cocnm-21-64-g001.jpg

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