ArticleCell & bioscience2023
SEPT2 crotonylation promotes metastasis and recurrence in hepatocellular carcinoma and is associated with poor survival.
Article in Cell & bioscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
- Mechanistic and functional integration of sirtuin deacylases: from substrate specificity to biological outcomes.Glycoconjugate journal · 2026Review
- CPT1B K321 crotonylation contributes to cardiac dysfunction in endotoxic shock.Experimental & molecular medicine · 2026Article
- HDAC1-mediated CDK1 decrotonylation inhibits colorectal cancer proliferation by regulating cell cycle and apoptosis.Frontiers in oncology · 2026Article
- Exploration of the Immune Microenvironment of Melanoma and Construction of Prognostic Models Based on the Expression Profile of Lysine Crotonylation-Related Genes.International journal of general medicine · 2026Article
- Protein crotonylation in cancer: mechanisms, functions, and therapeutic potential.Cell biology and toxicology · 2025Review
- Identification of lysine crotonylation-driven molecular clusters and immune dysregulation in HBV-related hepatocellular carcinoma via bioinformatics and machine learning.Translational cancer research · 2025Article
- Post-translational modifications in hepatocellular carcinoma: mechanisms and therapeutic potential.Medical oncology (Northwood, London, England) · 2025Review
- Short-chain acyl post-translational modifications in cancers: Mechanisms, roles, and therapeutic implications.Cancer communications (London, England) · 2025Review
- Machine learning model in multi-omics perspective demystifies the prognostic significance of crotonylation heterogeneity in clear cell renal cell carcinoma.BMC urology · 2025Article
- Acyl post-translational modification of proteins by metabolites in cancer cells.Cell death discovery · 2025Review
- Histone crotonylation in tumors (Review).Molecular and clinical oncology · 2025Review
- Lysine crotonylation in disease: mechanisms, biological functions and therapeutic targets.Epigenetics & chromatin · 2025Review
- Identification of proteome-wide and functional analysis of lysine crotonylation in multiple organs of the human fetus.Proteome science · 2025Article
- Cracking Lysine Crotonylation (Kcr): Enlightening a Promising Post-Translational Modification.Chembiochem : a European journal of chemical biology · 2025Review
- Characterization of lysine crotonylation-related lncRNAs for prognostic assessment and immune response in glioma.Frontiers in pharmacology · 2025Article
- Integrated analysis of single-cell and bulk transcriptomics reveals the prognostic value and underlying mechanisms of crotonylation in ovarian cancer.Frontiers in immunology · 2025Article
- Characterization of lactylation modification subtypes and the promoting role of CCL20 in hepatocellular carcinoma progression.Frontiers in genetics · 2025Article
- Review
- Integrative transcriptome analysis identifies a crotonylation gene signature for predicting prognosis and drug sensitivity in hepatocellular carcinoma.Journal of cellular and molecular medicine · 2024Article
- Protein lysine crotonylation in cellular processions and disease associations.Genes & diseases · 2024Review
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Authors and funding
9 authors at 3 institutions in 1 country.
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Abstract
backgroundHepatocellular carcinoma (HCC) metastasis and recurrence lead to therapy failure, which are closely associated with the proteome. However, the role of post-translational modification (PTM) in HCC, especially for the recently discovered lysine crotonylation (Kcr), is elusive.
resultsWe investigated the correlation between crotonylation and HCC in 100 tumor tissues and performed stable isotope labeling by amino acids and liquid chromatography tandem mass spectrometry in HCC cells, and we found that crotonylation was positively correlated with HCC metastasis, and higher crotonylation in HCC cells facilitated cell invasiveness. Through bioinformatic analysis, we found that the crotonylated protein SEPT2 was significantly hypercrotonylated in highly invasive cells, while the decrotonylated mutation of SEPT2-K74 impaired SEPT2 GTPase activity and inhibited HCC metastasis in vitro and in vivo. Mechanistically, SIRT2 decrotonylated SEPT2, and P85α was found to be the downstream effector of SEPT2. Moreover, we identified that SEPT2-K74cr was correlated with poor prognosis and recurrence in HCC patients, thus indicating its clinical potential as an independent prognostic factor.
conclusionsWe revealed the role of nonhistone protein crotonylation in regulating HCC metastasis and invasion. Crotonylation facilitated cell invasion through the crotonylated SEPT2-K74-P85α-AKT pathway. High SEPT2-K74 crotonylation predicted poor prognosis and a high recurrence rate in HCC patients. Our study revealed a novel role of crotonylation in promoting HCC metastasis.
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