ArticleCell death & disease2019
Targeting HIBCH to reprogram valine metabolism for the treatment of colorectal cancer.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- MetaGSCA: A tool for meta-analysis of gene set differential coexpression.PLoS computational biology · 2021Pooled it
- NMR-based metabolomics combined with metabolic pathway analysis reveals metabolic heterogeneity of colorectal cancer tissue at different anatomical locations and stages.International journal of cancer · 2025Article
- Altered metabolic profiles in colon and rectal cancer.Scientific reports · 2025Article
- Selective inhibition of TGF-β-induced epithelial-mesenchymal transition overcomes chemotherapy resistance in high-risk lung squamous cell carcinoma.Communications biology · 2025Article
- Role of amino acid metabolism in tumor immune microenvironment of colorectal cancer.American journal of cancer research · 2025Review
- Novel lipid metabolism factor HIBCH inhibitor synergizes with doxorubicin to suppress osteosarcoma growth and impacts clinical prognosis in osteosarcoma patients.Journal of bone oncology · 2024Article
- Targeting valine catabolism to inhibit metabolic reprogramming in prostate cancer.Cell death & disease · 2024Article
- Proteomics Analysis of Interactions between Drug-Resistant and Drug-Sensitive Cancer Cells: Comparative Studies of Monoculture and Coculture Cell Systems.Journal of proteome research · 2024Article
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- Valine metabolite, 3-hydroxyisobutyrate, promotes lipid metabolism and cell proliferation in porcine mammary gland epithelial cells.Frontiers in nutrition · 2024Article
- Mitochondrial dysfunction and onset of type 2 diabetes along with its complications: a multi-omics Mendelian randomization and colocalization study.Frontiers in endocrinology · 2024Article
- Multiomic analysis of lactylation and mitochondria-related genes in hepatocellular carcinoma identified MRPL3 as a new prognostic biomarker.Frontiers in oncology · 2024Article
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- Synergistic interactions of cytarabine-adavosertib in leukemic cell lines proliferation and metabolomic endpoints.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Peripheral Blood Serum NMR Metabolomics Is a Powerful Tool to Discriminate Benign and Malignant Ovarian Tumors.Metabolites · 2023Article
- Prognostic and tumor microenvironmental feature of clear cell renal cell carcinoma revealed by m6A and lactylation modification-related genes.Frontiers in immunology · 2023Article
- Exploration of prognosis and immunometabolism landscapes in ER+ breast cancer based on a novel lipid metabolism-related signature.Frontiers in immunology · 2023Article
- Correlation between amino acid metabolism and self-renewal of cancer stem cells: Perspectives in cancer therapy.World journal of stem cells · 2022Review
- Inhibiting BCKDK in triple negative breast cancer suppresses protein translation, impairs mitochondrial function, and potentiates doxorubicin cytotoxicity.Cell death discovery · 2021Article
- Regulation of signal transduction pathways in colorectal cancer: implications for therapeutic resistance.PeerJ · 2021Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Valine catabolism is known to be essential for cancer cells but the detailed mechanism remains unclear. This study is to explore the critical roles of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) in colorectal cancers (CRC) and to develop a new therapy returning valine metabolism homeostasis. High HIBCH expression was first confirmed to correlate with poor survival in patients with CRC, which was then linked to the increased cell growth, resistant apoptosis, and decreased autophagy in CRC cells. The functions of HIBCH in CRC were dependent on its mitochondrial localization. High HIBCH level was further demonstrated to promote the metabolism of tricarboxylic acid cycle as well as oxidative phosphorylation in CRC cells. Based on above findings, we further discovered a novel valine catabolism inhibitor SBF-1. The pharmacological blockade of HIBCH mitochondrial localization with SBF-1 resulted in decreased cancer cell growth and increased autophagy, collectively contributing to the antitumor effect both in vitro and in vivo. Moreover, anti-VEGF therapy with bevacizumab increased HIBCH level in CRC cells, which in turn caused the resistance to the therapy. The interference with HIBCH function by SBF-1 significantly increased the antitumor efficacy of bevacizumab and led to a robust survival benefit. The present study identified HIBCH as a critical enzyme of valine catabolism in CRC progression and resistance to anti-VEGF therapy. We also provided a novel HIBCH inhibitor SBF-1, which highlighted the combined therapy using valine catabolic inhibitor along with anti-VEGF drugs, to control progression of CRC.
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