BCAT1 (Branched Chain Amino Acid Transaminase 1 )

Bisulfite conversion has higher DNA methylation levels for certain CRC biomarkers in tumor tissues, suggesting over-estimation of methylation that could affect biomarker specificity.

The paradoxical role of BCAAs in modulating anti-tumor immunity is examined alongside the potential of dietary modulation and the development of pharmacological inhibitors targeting this pathway. Concluding perspectives highlight the trajectory for translating these insights into precision oncology, advocating for biomarker-guided and context-specific therapeutic strategies.

Strategies targeting BCATs, including enzyme inhibitors, dietary BCAA restriction, and combination therapies, have shown the potential to overcome drug resistance and improve treatment outcomes. This review synthesizes current knowledge on the mechanisms of BCATs in cancer progression and resistance, providing a foundation for future research and clinical applications.

UMP binds to vimentin and protects it against ubiquitination-proteasome degradation. Dietary BCAA restriction or blockade of UMP biosynthesis impaired cancer spread of BCAT1-high CRC, and BCAT1-to-BCAT2 expression ratio is an independent prognostic factor in CRC and pan-cancer cohorts, highlighting translational relevance of BCAA metabolic compartmentalization in cancer metastasis.

Targeting BCAT1 or disrupting its downstream mTOR/NF-κB signaling effectively inhibits PDAC pan-metastasis. These results uncover an unrecognized metabolic-immune crosstalk governing BCAT1+ metastasis-related tumor cells and pan-metastasis of PDAC.

Proof-of-principle experiments assessed CRC cell lines for BCAT1/IKZF1 methylation after irradiation and 5-fluorouracil treatment...Reduced BCAT1/IKZF1 methylation in rectal tumors and plasma ctDNA reflects reductions in tumor cellularity. These data support future investigations to use methylated BCAT1/IKZF1 ctDNA for monitoring response to neoadjuvant therapy in patients with rectal cancer.

Multivariate analysis further identified tumor size (OR = 1.974, 95% CI: 1.321-2.950, P = 0.005) and TNM stage (OR = 2.117, 95% CI: 1.452-3.087, P = 0.002) as independent predictors of multi-gene methylation positivity. Multi-gene methylation detection showed high diagnostic value for CRC and may serve as a valuable adjunct tool in CRC screening strategies.

The diagnostic sensitivities of the model for CRC of different stages were 85.71% for stage Ⅰ, 92.86% for stage Ⅱ, 78.95% for stage Ⅲ, and 87.50% for unstaged cases. A diagnostic model based on the methylation levels of the SEPTIN9, BCAT1, IKZF1, BCAN, and VAV3 genes in plasma demonstrates good diagnostic performance for CRC, particularly in early-stage cases.

DNA methylation and microRNA biomarkers hold strong promises for non-invasive CRC screening. Multi-marker panels demonstrate superior diagnostic accuracy and may provide a cost-effective, scalable approach for early CRC detection in resource-limited settings.

MAT2A, BCAT1 and GCLM were selected for small interfering RNA experiments and the results exhibited that apoptosis rates significantly promoted in HL60/R when MAT2A, BCAT1 or GCLM were interfered. An integrative analysis of proteomic and metabolomic data revealed significant disruptions in amino acid metabolism in HL60/R cells, including the metabolic pathways of alanine, aspartate and glutamate, cysteine and methionine, as well as glutathione metabolism.

Innovative therapeutic strategies targeting BCAA pathways-ranging from selective small-molecule inhibitors (e.g., LAT1 and BCAT1/2) to dietary modulation-have shown promising preclinical and early clinical efficacy, highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses. By integrating multi-omics data and precision targeting approaches, this review underscores the translational significance of BCAA metabolic reprogramming, positioning it as a novel frontier in cancer treatment.