ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Loss of LRP1 Promotes Hepatocellular Carcinoma Progression via UFL1-Mediated Activation of NF-κB Signaling.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-wide association susceptibility loci for cluster headache support a role for inflammation in the pathophysiology.The journal of headache and pain · 2026Pooled it
- LRP1 Activation Promotes Metabolic Reprogramming and Mrc1 Expression to Attenuate LPS-Induced Cognitive Deficits: An Integrated Omics Analysis.CNS neuroscience & therapeutics · 2026Article
- NF-κB signaling in hepatocellular carcinoma: Mechanisms of tumor progression, immune evasion, and therapeutic resistance.Translational oncology · 2026Review
- Gitogenin impedes tumorigenesis in hepatocellular carcinomaFrontiers in oncology · 2026Article
- piR-43452 suppresses bladder cancer progression and enhances gemcitabine sensitivity via GTSF1/PIWIL4-mediated LRP1 mRNA destabilization.Translational oncology · 2026Article
- Loss of UFL1 confers enzalutamide resistance of prostate tumors by regulating METTL16-mediated m6A modification of EEF1A1 mRNA.International journal of biological sciences · 2026Article
- NKAP overexpression promotes gastric cancer immune escape by inducing IL-10 secretion from mature dendritic cells during anti-PD-L1 therapy.Journal of gastrointestinal oncology · 2025Article
- The Role of UFMylation in the Development and Progression of Gastric Cancer.Oncology research · 2025Review
- Loss of LRP1 Promotes Hepatocellular Carcinoma Progression via UFL1-Mediated Activation of NF-κB Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Low-density lipoprotein receptor-related protein-1 (LRP1) is thought to be correlated with hepatocellular carcinoma (HCC) invasion and metastasis. However, the precise mechanism through which LRP1 contributes to HCC progression remains unclear. Here, lower LRP1 levels are associated with malignant progression, and poor prognosis in patients with HCC is shown. LRP1 knockdown enhances the tumorigenicity of HCC cells in vitro and in vivo, whereas overexpression of either LRP1 or its β-chain has the opposite effect. Mechanistically, LRP1 knockdown promotes the binding of ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) to OGA and accelerates ubiquitin-mediated OGA degradation, leading to increased O-GlcNAcylation of nuclear factor-kappa B (NF-κB) and subsequent inhibition of pro-apoptotic gene expression. Conversely, exogenously expressed truncated β-chain (β∆) stabilizes OGA by disrupting the association between UFL1 and OGA, consequently abolishing the anti-apoptotic effects of O-GlcNAcylated NF-κB. The findings identify LRP1, particularly its β-chain, as a novel upstream control factor that facilitates the stabilization of the OGA protein, thereby suppressing NF-κB signaling and attenuating HCC progression, thus suggesting a novel therapeutic strategy for HCC.
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