ArticleCell death & disease2022
Galectin-1 confers resistance to doxorubicin in hepatocellular carcinoma cells through modulation of P-glycoprotein expression.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Circulating galectin-1 delineates response to bevacizumab in melanoma patients and reprograms endothelial cell biology.Proceedings of the National Academy of Sciences of the United States of America · 2023Trial
- The role of galectins in modulating the tumor microenvironment and driving metastasis in skin cancers.Biological research · 2026Review
- Galectin-1 modulates glycolysis through a GM1-galactose-dependent pathway to promote hyperthermia resistance in HCC.Hepatology (Baltimore, Md.) · 2026Article
- 2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression.Scientific reports · 2026Article
- Galectins at the crossroads of tumor immunity, metabolism, and metastasis: mechanisms, therapeutic resistance, and translational opportunities.Frontiers in immunology · 2026Review
- The Immunomodulatory Role of Galectin-1 in the Tumour Microenvironment and Strategies for Therapeutic Applications.Cancers · 2025Review
- Acridine-Based Chalcone 1C and ABC Transporters.International journal of molecular sciences · 2025Article
- A Bioinert Hydrogel Framework for Precision 3D Cell Cultures: Advancing Automated High-Content and High-Throughput Drug Screening.Small science · 2025Article
- EZH2: From Oncogenic Driver to Therapeutic Target for Overcoming Drug Resistance in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2025Review
- Engineered 3D liver-tissue model with minispheroids formed by a bioprinting process supported withBioactive materials · 2024Article
- MiRNAs function in the development of resistance against doxorubicin in cancer cells: targeting ABC transporters.Frontiers in pharmacology · 2024Review
- Regulation of Nrf2/Keap1 signaling pathway in cancer drug resistance by galectin-1: cellular and molecular implications.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Integrin α6β4 Confers Doxorubicin Resistance in Cancer Cells by Suppressing Caspase-3-Mediated Apoptosis: Involvement of N-Glycans on β4 Integrin Subunit.Biomolecules · 2023Article
- Study Models of Drug-Drug Interactions Involving P-Glycoprotein: The Potential Benefit of P-Glycoprotein Modulation at the Kidney and Intestinal Levels.Molecules (Basel, Switzerland) · 2023Review
- Galectin-1-mediated high NCAPG expression correlates with poor prognosis in gastric cancer.Aging · 2023Article
- siRNA and targeted delivery systems in breast cancer therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Targeting galectin-driven regulatory circuits in cancer and fibrosis.Nature reviews. Drug discovery · 2023Review
- The Blessed Union of Glycobiology and Immunology: A Marriage That Worked.Medicines (Basel, Switzerland) · 2023Review
- Inhibition of JNK/c-Jun-ATF2 Overcomes Cisplatin Resistance in Liver Cancer through down-Regulating Galectin-1.International journal of biological sciences · 2023Article
- Leverage biomaterials to modulate immunity for type 1 diabetes.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Galectin-1 (GAL1), a β-galactoside-binding protein abundantly expressed in the tumor microenvironment, has emerged as a key mechanism of chemoresistance developed by different tumors. Although increased expression of GAL1 is a hallmark of hepatocellular carcinoma (HCC) progression, aggressiveness and metastasis, limited information is available on the role of this endogenous lectin in HCC resistance to chemotherapy. Moreover, the precise mechanisms underlying this effect are uncertain. HCC has evolved different mechanisms of resistance to chemotherapy including those involving the P-glycoprotein (P-gp), an ATP-dependent drug efflux pump, which controls intracellular drug concentration. Here, we investigated the molecular mechanism underlying GAL1-mediated chemoresistance in HCC cells, particularly the involvement of P-gp in this effect. Our results show that GAL1 protected HepG2 cells from doxorubicin (DOX)- and sorafenib-induced cell death in vitro. Accordingly, GAL1-overexpressing HepG2 cells generated DOX-resistant tumors in vivo. High expression of GAL1 in HepG2 cells reduced intracellular accumulation of DOX likely by increasing P-gp protein expression rather than altering its membrane localization. GAL1-mediated increase of P-gp expression involved activation of the phosphatidylinositol-3 kinase (PI3K) signaling pathway. Moreover, 'loss-of-function' experiments revealed that P-gp mediates GAL1-driven resistance to DOX, but not to sorafenib, in HepG2 cells. Conversely, in PLC/PRF/5 cells, P-gp protein expression was undetectable and GAL1 did not control resistance to DOX or sorafenib, supporting the critical role of P-gp in mediating GAL1 effects. Collectively, our findings suggest that GAL1 confers chemoresistance in HCC through mechanisms involving modulation of P-gp, thus emphasizing the role of this lectin as a potential therapeutic target in HCC.
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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.