ArticleCell death & disease2018
Galunisertib suppresses the staminal phenotype in hepatocellular carcinoma by modulating CD44 expression.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- Chemoresistance: The hidden barrier in cancer treatment.Cancer pathogenesis and therapy · 2026Review
- Proteoglycan-4 potentiates the antitumor efficacy of regorafenib in an orthotopic model of hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- New Experimental Mouse Models to Evaluate the Role of Transforming Growth Factor-Beta in Liver Tumorigenesis.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.Cell death & disease · 2025Review
- Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics.MedComm · 2025Review
- 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
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
- Bioengineered Organoids Offer New Possibilities for Liver Cancer Studies: A Review of Key Milestones and Challenges.Bioengineering (Basel, Switzerland) · 2024Review
- The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis.International journal of biological sciences · 2024Review
- Hepatitis B virus X protein and TGF-β: partners in the carcinogenic journey of hepatocellular carcinoma.Frontiers in oncology · 2024Review
- Circular RNA cFAM210A, degradable by HBx, inhibits HCC tumorigenesis by suppressing YBX1 transactivation.Experimental & molecular medicine · 2023Article
- Transcriptomic evidence for tumor-specific beneficial or adverse effects of TGFβ pathway inhibition on the prognosis of patients with liver cancer.FEBS open bio · 2023Article
- Genetic heterogeneity of liver cancer stem cells.Anatomy & cell biology · 2023Article
- Potential Molecular Targeted Therapy for Unresectable Hepatocellular Carcinoma.Current oncology (Toronto, Ont.) · 2023Review
- Microfluidic-Assisted Production of Gastro-Resistant Active-Targeted Diatomite Nanoparticles for the Local Release of Galunisertib in Metastatic Colorectal Cancer Cells.Advanced healthcare materials · 2023Article
- TGF-beta signal transduction: biology, function and therapy for diseases.Molecular biomedicine · 2022Review
- The Tumor Microenvironment Drives Intrahepatic Cholangiocarcinoma Progression.International journal of molecular sciences · 2022Article
- Proteoglycans in Cancer: Friends or Enemies? A Special Focus on Hepatocellular Carcinoma.Cancers · 2022Review
- TGF-β Signaling in Liver, Pancreas, and Gastrointestinal Diseases and Cancer.Gastroenterology · 2021Review
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem cells (CSCs) niche in the tumor microenvironment is responsible for cancer recurrence and therapy failure. To better understand its molecular and biological involvement in hepatocellular carcinoma (HCC) progression, one can design more effective therapies and tailored then to individual patients. While sorafenib is currently the only approved drug for first-line treatment of advanced stage HCC, its role in modulating the CSC niche is estimated to be small. By contrast, transforming growth factor (TGF)-β pathway seems to influence the CSC and thus may impact hallmarks of HCC, such as liver fibrosis, cirrhosis, and tumor progression. Therefore, blocking this pathway may offer an appealing and druggable target. In our study, we have used galunisertib (LY2157299), a selective ATP-mimetic inhibitor of TGF-β receptor I (TGFβI/ALK5) activation, currently under clinical investigation in HCC patients. Because the drug resistance is mainly mediated by CSCs, we tested the effects of galunisertib on stemness phenotype in HCC cells to determine whether TGF-β signaling modulates CSC niche and drug resistance. Galunisertib modulated the expression of stemness-related genes only in the invasive (HLE and HLF) HCC cells inducing a decreased expression of CD44 and THY1. Furthermore, galunisertib also reduced the stemness-related functions of invasive HCC cells decreasing the formation of colonies, liver spheroids and invasive growth ability. Interestingly, CD44 loss of function mimicked the galunisertib effects on HCC stemness-related functions. Galunisertib treatment also reduced the expression of stemness-related genes in ex vivo human HCC specimens. Our observations are the first evidence that galunisertib effectiveness overcomes stemness-derived aggressiveness via decreased expression CD44 and THY1.
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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.