ArticleCell death & disease2021
BCAT1 decreases the sensitivity of cancer cells to cisplatin by regulating mTOR-mediated autophagy via branched-chain amino acid metabolism.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- A systematic review of omics discovery studies to identify pertinent metabolic pathways for locally advanced rectal cancer in response to neoadjuvant chemoradiotherapy.Metabolomics : Official journal of the Metabolomic Society · 2025Pooled it
- Restores Aβ Clearance by Overcoming PCSK9-LRP1 Dysregulation and TRIB3-Mediated Autophagy Blockade in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- miR-142-3p in cancer: intracellular tumor suppression and extracellular vesicle- mediated microenvironmental signaling.Molecular biology reports · 2026Review
- BCAT1-dependent HIF-1α stabilization is a targetable metabolic vulnerability in hepatocellular carcinoma.Cell reports. Medicine · 2026Article
- The BCAA metabolism-related gene BCAT1 promotes the progression of bladder urothelial carcinoma through the PI3K/AKT/mTOR signalling pathway.Functional & integrative genomics · 2026Article
- Amino Acid Metabolism-Related Gene Kynureninase (KYNU) as a Prognostic Predictor and Regulator of Diffuse Large B-Cell Lymphoma.Biochemical genetics · 2026Article
- Metabolic characteristics in hepatocellular carcinoma: amino acid metabolic reprogramming.Molecular cancer · 2026Review
- Branched-chain amino acid transaminases as promising targets in tumor therapy.Frontiers in cell and developmental biology · 2026Review
- Deciphering macrophage heterogeneity and factors driving M2 polarization in lung adenocarcinoma through single-cell RNA sequencing.Apoptosis : an international journal on programmed cell death · 2025Article
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- Review
- Multiple roles of branched-chain amino acid metabolism in tumour progression.Journal of biomedical science · 2025Review
- BCAT1 is a NOTCH1 target and sustains the oncogenic function of NOTCH1.Haematologica · 2025Article
- Identification and validation of a metabolic-related gene risk model predicting the prognosis of lung, colon, and breast cancers.Scientific reports · 2025Article
- Identification of amino acid metabolism-related gene Leucyl-tRNA synthetase 1 (LARS1) as a potential prognostic and therapeutic target in hepatocellular carcinoma.Frontiers in oncology · 2025Article
- BCAA metabolism: the Achilles' heel of ovarian cancer, polycystic ovary syndrome, and premature ovarian failure.Frontiers in endocrinology · 2025Review
- BCAA metabolism in cancer progression and therapy resistance: The balance between fuel and cell signaling.Frontiers in pharmacology · 2025Review
- Mitochondrial dynamics in cisplatin resistance: molecular mechanisms and therapeutic targeting.Frontiers in oncology · 2025Review
- Review
- Targeting autophagy promotes the antitumor effect of radiotherapy on cervical cancer cells.Cancer biology & therapy · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cisplatin is one of the most effective chemotherapy drugs and is widely used in the treatment of cancer, including hepatocellular carcinoma (HCC) and cervical cancer, but its therapeutic benefit is limited by the development of resistance. Our previous studies demonstrated that BCAT1 promoted cell proliferation and decreased cisplatin sensitivity in HCC cells. However, the exact role and mechanism of how BCAT1 is involved in cisplatin cytotoxicity remain undefined. In this study, we revealed that cisplatin triggered autophagy in cancer cells, with an increase in BCAT1 expression. The cisplatin-induced up-regulation of BCAT1 decreased the cisplatin sensitivity by regulating autophagy through the mTOR signaling pathway. In addition, branched-chain amino acids or leucine treatment inhibited cisplatin- or BCAT1-mediated autophagy and increased cisplatin sensitivity by activating mTOR signaling in cancer cells. Moreover, inhibition of autophagy by chloroquine increased cisplatin sensitivity in vivo. Also, the knockdown of BCAT1 or the administration of leucine activated mTOR signaling, inhibited autophagy, and increased cisplatin sensitivity in cancer cells in vivo. These findings demonstrate a new mechanism, revealing that BCAT1 decreases cisplatin sensitivity in cancer cells by inducing mTOR-mediated autophagy via branched-chain amino acid leucine metabolism, providing an attractive pharmacological target to improve the effectiveness of chemotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.