ArticleClinical and translational medicine2026
Feedback regulation between histone H3 lysine 18 lactylation and TROP2-mediated glycolysis drives metastatic progression of colorectal cancer.
Article in Clinical and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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
5 citing papers in PubMed.
- Preclinical Pharmacological Evaluation of Sacituzumab Govitecan (IMMU-132) in TROP2-Positive Colorectal Liver Metastasis Models.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Overcoming ADC resistance in advanced colorectal cancer by dual targeting of TROP2 and PERK to suppress Wnt/β-catenin signaling.Cell reports. Medicine · 2026Article
- Feedback regulation between histone H3 lysine 18 lactylation and TROP2-mediated glycolysis drives metastatic progression of colorectal cancer.Clinical and translational medicine · 2026Article
- Metabolic-epigenetic crosstalk in latent autoimmune diabetes in adults: potential roles of lactate-induced histone lactylation in immune regulation and pancreatic β-cell fate.Frontiers in endocrinology · 2026Review
- YBX1 as an adaptive RNA hub in cancer: linking state-dependent RNA regulation to tumor immunity, metabolic reprogramming, and therapy resistance.Frontiers in immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
Abstract
backgroundTROP2, a critical cell surface oncogenic signal transducer, is increasingly linked to refractory metastatic colorectal cancer (CRC) and other solid tumours. Robust lactate accumulation within metastatic niches correlates with pathological metastatic progression. Anti-TROP2 antibody-drug conjugates (ADCs) are clinically available but show limited efficacy in advanced metastatic CRC. Elucidating how TROP2 signalling orchestrates molecular and cellular programs enabling CRC metastatic progression would help improve metastasis therapies.
methodsTissue microarray, immunohistochemistry, and western blotting delineated TROP2's pathological role in CRC liver metastasis (CRLM). Metabolomics characterised TROP2-mediated metabolic effect. Western blot detected TROP2 responsive lactylation sites. Cell-derived xenograft (CDX), intra-splenic injection models, and patient-derived xenografts (PDX) validated TROP2 or TROP2-induced H3K18 lactylation (H3K18la) in CRLM pathogenesis and Acriflavine therapeutic response. Genome-wide H3K18la profiling was performed by ChIP-seq.
resultsHere, we identify a self-reinforcing positive feedback loop between H3K18la and TROP2 in CRC cells that drives CRC metastatic progression. We show that TROP2 is elevated during CRC metastatic process, with high TROP2 levels in liver metastases predicting increased post-therapy recurrence in two distinct cohorts. We find that H3K18la levels are upregulated in CRC cells in response to TROP2 expression level. TROP2 promotes robust lactate production via the YBX1-HIF-1α signal axis. Targeting glycolytic flux decreases H3K18 lactylation and curbs TROP2-driven CRLM colonisation and progression. Mechanistically, ChIP-seq detection reveals H3K18la deposition at a set of pro-metastatic gene promoters, promoting their expression. Crucially, TROP2-induced H3K18la is found in turn sustaining TROP2 expression, forming a positive feedback loop that further accelerated metastatic progression. Pharmacologic HIF-1α inhibition with acriflavine, an old FDA-approved agent, suppresses TROP2-high CRLM progression in multiple pre-clinical models.
conclusionsCollectively, we establish H3K18la as a crucial epigenetic driver of TROP2-mediated CRLM progression and propose that disrupting the H3K18la-TROP2 feedback loop offers a novel therapeutic strategy against CRC metastasis. KEY POINTS: H3K18la is specifically increased in CRC cells in response to TROP2 signalling and drives TROP2-mediated CRLM progression Genome-wide analysis shows H3K18la deposition at the promoters of metastasis-promoting genes drives their expression in TROP2-high CRC. Lactate sustains TROP2 expression in CRC cells via H3K18la Acriflavine suppresses TROP2-driven CRLM by targeting the H3K18la/TROP2 feedback loop.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.