ArticleClinical and translational medicine2026
ATF6-mediated GTPase RHOQ promotes liver cancer progression via enhancing aerobic glycolysis through PAK1 phosphorylation.
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. 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
6 authors.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) ranks among the most prevalent malignant tumours worldwide, accounting for approximately 90% of primary liver cancer cases, with the highest incidence observed in Asia. Activating Transcription Factor 6 (ATF6) is an endoplasmic reticulum stress-responsive transcription factor. Our previous studies have demonstrated that ATF6 contributes to HCC tumourigenesis and progression through signalling pathways such as ATF6-CTH-Keap1-mTORC1 and ATF6-PPM1H-RPS6KB1.
methodsRNA sequencing identified ATF6 transcriptional targets, with Ras homolog family member Q (RHOQ) validation via chromatin immunoprecipitation and electrophoretic mobility shift assay. RHOQ expression and clinical significance were analysed in HCC cohorts. Functional assays assessed proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). Tumour growth was evaluated in orthotopic (NOG mice) and subcutaneous (nude mice) models. Mechanistic analyses were performed to characterise RHOQ-mediated regulation of p21-activated kinase 1 (PAK1) signalling and metabolic remodelling. Furthermore, therapeutic synergy between PAK1 inhibitor IPA-3 and Glypican-3 (GPC3)-CAR T cells was tested.
resultsWe identified RHOQ as a direct transcriptional target of ATF6. Clinically, elevated RHOQ expression correlated with poorer progression-free survival (PFS) in patients with HCC. Functionally, RHOQ promoted the proliferation and metastasis of liver tumour cells. Correspondingly, RHOQ knockdown markedly suppressed tumour growth in xenograft models, with consistent results observed in a hydrodynamic tail vein injection(HTVi) model. Mechanistic investigations revealed that RHOQ directly bound to PAK1, promoted its phosphorylation and activation and thereby drove aerobic glycolysis in liver tumour cells. Furthermore, combined treatment with the PAK1-specific inhibitor IPA-3 and GPC3-targeted CAR T-cell therapy produced a significant synergistic anti-tumour effect.
conclusionIn summary, this study systematically delineated the importance of the ATF6-RHOQ-PAK1 signalling cascade in driving liver cancer progression and provided a rationale for the design of targeted combination therapies. HIGHLIGHTS: RHOQ is a novel direct transcriptional target of ATF6 in HCC. High RHOQ expression is associated with unfavourable clinicopathological features and poorer PFS. RHOQ drives HCC progression via PAK1 activation and aerobic glycolysis. Combining the PAK1-specific inhibitor IPA-3 with GPC3-targeted CAR T-cell therapy produces a potent synergistic anti-tumour effect.
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.