ArticleJournal of translational medicine2026
The HKDC1-ASS1-ACSBG2 axis reprograms lipid metabolism to drive therapeutic resistance in hepatocellular carcinoma.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is a lethal malignancy characterized by profound metabolic reprogramming, notably aberrant lipid metabolism. Current therapeutic strategies offer limited efficacy, highlighting the critical need to identify its metabolic vulnerabilities. This study aims to investigate the role of the HKDC1-ASS1-ACSBG2 axis in lipid metabolic reprogramming and therapeutic resistance in HCC.
methodsUsing clinical HCC specimens and cell lines, we systematically evaluated the functions and mechanisms of HKDC1, ASS1, and ACSBG2 in lipogenesis, cell proliferation, and drug response via RNA sequencing, co-immunoprecipitation, immunofluorescence, ubiquitination assays, dual-luciferase reporter assays, cellular functional experiments, and nude mouse xenograft models.
resultsHKDC1 was highly expressed in HCC and correlated with poor patient prognosis. Mechanistically, HKDC1 interacts with ASS1 (310–412 aa) via its HKLS1 domain, inhibiting ubiquitin-mediated degradation and stabilizing ASS1. This enhances the production of glutamine-derived acetyl-CoA. The accumulated acetyl-CoA transcriptionally activates ACSBG2 by inducing histone H3 acetylation, thereby driving lipid biosynthesis and HCC cell proliferation. This axis operates distinctly from the FASN-dependent pathway and promotes lenvatinib resistance both in vitro and in vivo.
conclusionOur study unveils a novel metabolic regulatory axis, HKDC1-ASS1-ACSBG2, that promotes lipogenesis and tumor progression in HCC by integrating multiple metabolic pathways, and confers lenvatinib resistance. Targeting this axis may present a novel therapeutic strategy to overcome treatment resistance in this recalcitrant malignancy.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.