BCAT1调控乳腺癌代谢重编程的分子机制研究进展
Research Progress on the Molecular Mechanisms of BCAT1-Regulated Metabolic Reprogramming in Breast Cancer
DOI: 10.12677/acm.2026.1693269, PDF,   
作者: 马 旭*：延安大学延安医学院，陕西 延安；杨喜明：延安大学附属医院烧伤整形手外科，陕西 延安
关键词: BCAT1；乳腺癌；代谢重编程；支链氨基酸；mTOR信号通路；三阴性乳腺癌；治疗靶点；BCAT1； Breast Cancer； Metabolic Reprogramming； Branched-Chain Amino Acids； mTOR Signaling Pathway； Triple-Negative Breast Cancer； Therapeutic Target
摘要: 支链氨基酸转氨酶(BCAT1)是支链氨基酸(BCAA)代谢的关键限速酶，近年来被发现广泛参与多种恶性肿瘤的代谢重编程。本文系统综述了BCAT1在乳腺癌，尤其是三阴性乳腺癌(TNBC)和HER2阳性亚型中的异常高表达及其临床相关性，并重点阐述了BCAT1调控乳腺癌代谢重编程的核心分子机制，包括激活mTOR信号通路、双向调控糖酵解与线粒体氧化磷酸化、以及通过表观遗传修饰影响能量代谢。进一步，本文构建了BCAT1介导的“代谢–表观–信号”多维功能调控网络，涵盖其与Twist/Foxc1、SOX2、Wnt/Myc及c-Myc等关键信号轴和转录因子的交互作用。本文新设立章节深入讨论了BCAT1在不同癌种及乳腺癌亚型中潜在的双重功能矛盾，并从酶活性定位、氧化还原状态、α-酮戊二酸(α-KG)桥接及细胞情境依赖性等角度提出解释，同时整合了其通过CXXC基序维持有丝分裂保真度的非代谢功能与代谢重编程之间的潜在联系，提出“代谢–基因组稳定”功能转换假说。在转化研究层面，BCAT1展现出作为预后生物标志物和治疗靶点的潜力，基于BCAT1-mTOR轴的联合治疗策略(如联合mTOR抑制剂、铁死亡诱导剂或免疫检查点阻断剂)为克服乳腺癌治疗抵抗提供了新思路。最后，本文讨论了当前研究中存在的亚型功能异质性、代谢与免疫微环境互作机制不清以及临床转化差距等挑战，并提出未来应聚焦于单细胞代谢异质性、表观遗传调控网络解析及双靶点联合治疗开发等方向。本综述为深入理解BCAT1在乳腺癌中的多功能调控作用及精准诊疗策略的制定提供了理论依据。
Abstract: Branched-chain amino acid transaminase 1 (BCAT1), a key rate-limiting enzyme in branched-chain amino acid (BCAA) metabolism, has recently been recognized as a critical player in metabolic reprogramming across various malignancies. This review systematically summarizes the aberrantly elevated expression of BCAT1 in breast cancer, particularly in triple-negative breast cancer (TNBC) and HER2-positive subtypes, along with its clinical relevance. We focus on the core molecular mechanisms by which BCAT1 regulates metabolic reprogramming in breast cancer, including activation of the mTOR signaling pathway, bidirectional regulation of glycolysis and mitochondrial oxidative phosphorylation, and epigenetic modification-mediated modulation of energy metabolism. Furthermore, we propose a multidimensional “metabolism-epigenetics-signaling” regulatory network mediated by BCAT1, highlighting its crosstalk with key signaling axes and transcription factors such as Twist/Foxc1, SOX2, Wnt/Myc, and c-Myc. In particular, this review establishes a dedicated section to deeply discuss the potential dual or contradictory functions of BCAT1 across different cancer types and breast cancer subtypes, offering possible explanations from perspectives including enzyme activity localization, redox status, α-ketoglutarate (α-KG) bridging, and cellular context dependency. Meanwhile, it integrates the non-metabolic function of BCAT1 in maintaining mitotic fidelity through its CXXC motif with its metabolic reprogramming role, proposing a “metabolism-genome stability” functional switch hypothesis. From a translational perspective, BCAT1 shows potential as a prognostic biomarker and therapeutic target. Combination strategies targeting the BCAT1-mTOR axis (e.g., combined with mTOR inhibitors, ferroptosis inducers, or immune checkpoint blockers) offer new avenues to overcome therapeutic resistance in breast cancer. Finally, we discuss current challenges, including subtypespecific functional heterogeneity, unclear interplay between metabolism and the immune microenvironment, and gaps in clinical translation. Future directions should focus on single-cell metabolic heterogeneity, systematic dissection of the epigenetic regulatory network, and development of dual-target combination therapies. This review provides a theoretical foundation for understanding the multifaceted roles of BCAT1 in breast cancer and for developing precision diagnostic and therapeutic strategies.
文章引用：马旭, 杨喜明. BCAT1调控乳腺癌代谢重编程的分子机制研究进展[J]. 临床医学进展, 2026, 16(9): 2250-2258. https://doi.org/10.12677/acm.2026.1693269

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