ArticleOncogenesis2019
LXRα limits TGFβ-dependent hepatocellular carcinoma associated fibroblast differentiation.
Article in Oncogenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
What it found
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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
30 citing papers in PubMed, 47 citations in OpenAlex.
- Role of liver X receptors in the pathogenesis and treatment of chronic liver disease (Review).Molecular medicine reports · 2026Review
- New Hepatocellular Carcinoma (HCC) Primary Cell Cultures as Models for Exploring Personalized Anti-TGF-β Therapies Based on Tumor Characteristics.International journal of molecular sciences · 2025Article
- Immunotherapy resistance in solid tumors: mechanisms and potential solutions.Cancer biology & therapy · 2024Review
- Pivotal role of intestinal cholesterol and nuclear receptor LXR in metabolic liver steatohepatitis and hepatocarcinoma.Cell & bioscience · 2024Article
- Activation of CTU2 expression by LXR promotes the development of hepatocellular carcinoma.Cell biology and toxicology · 2024Article
- scRNA-Seq Analysis Revealed CAFs Regulating HCC Cells via PTN Signaling.Journal of hepatocellular carcinoma · 2024Article
- Liver X Receptors (LXRs) in cancer-an Eagle's view on molecular insights and therapeutic opportunities.Frontiers in cell and developmental biology · 2024Review
- Dysregulated cholesterol regulatory genes in hepatocellular carcinoma.European journal of medical research · 2023Review
- Emerging Insights into Liver X Receptor α in the Tumorigenesis and Therapeutics of Human Cancers.Biomolecules · 2023Review
- Liver X receptor agonists exert antitumor effects against hepatocellular carcinoma via inducing REPS2 expression.Acta pharmacologica Sinica · 2023Article
- Emerging Role of Cancer-Associated Fibroblasts in Progression and Treatment of Hepatocellular Carcinoma.International journal of molecular sciences · 2023Review
- Influence of extracellular matrix composition on tumour cell behaviour in a biomimetic in vitro model for hepatocellular carcinoma.Scientific reports · 2023Article
- The origins, roles and therapies of cancer associated fibroblast in liver cancer.Frontiers in oncology · 2023Review
- Signaling pathways in cancer-associated fibroblasts: recent advances and future perspectives.Cancer communications (London, England) · 2023Review
- Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and Cholangiocarcinoma.Cellular and molecular gastroenterology and hepatology · 2023Review
- Advances of cancer-associated fibroblasts in liver cancer.Biomarker research · 2022Review
- The impact of the spatial heterogeneity of resistant cells and fibroblasts on treatment response.PLoS computational biology · 2022Article
- Identification of Lactate-Related Gene Signature for Prediction of Progression and Immunotherapeutic Response in Skin Cutaneous Melanoma.Frontiers in oncology · 2022Article
- Current Strategies for the Treatment of Hepatocellular Carcinoma by Modulating the Tumor Microenvironment via Nano-Delivery Systems: A Review.International journal of nanomedicine · 2022Review
- Cancer-associated fibroblasts: overview, progress, challenges, and directions.Cancer gene therapy · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Transforming growth factor β (TGFβ) is deposited in the extracellular space of diverse tissues. Resident fibroblasts respond to TGFβ and undergo myofibroblastic differentiation during tissue wound healing and cancer progression. Cancer-associated fibroblasts (CAFs) communicate with tumor cells during cancer progression, under the guidance of TGFβ signaling. We report that agonist-activated liver X receptors (LXR) limit the expression of key components of myofibroblast differentiation, including the α-smooth muscle actin (αSMA) gene in liver cancer cells. CAFs derived from hepatocellular carcinoma (HCC) express high αSMA and low LXRα levels, whereas hepatocarcinoma cells exhibit an inverse expression pattern. All hepatoma cells analyzed responded to the LXRα agonist T0901317 by inducing fatty acid synthase (FASN) expression. On the other hand, T0901317 antagonized TGFβ-induced fibroblastic marker responses, such as fibronectin and calponin, in a subset of hepatoma cells and all CAFs analyzed. Mechanistically, LXRα antagonized TGFβ signaling at the transcriptional level. Smad3 and LXRα were recruited to adjacent DNA motifs of the ACTA2 promoter. Upon cloning the human ACTA2 promoter, we confirmed its transcriptional induction by TGFβ stimulation, and LXRα overexpression repressed the promoter activity. Hepatosphere formation by HCC cells was enhanced upon co-culturing with CAFs. T0901317 suppressed the positive effects exerted on hepatosphere growth by CAFs. Taken together, the data suggest that LXRα agonists limit TGFβ-dependent CAF differentiation, potentially limiting primary HCC growth.
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.