ArticleHepatology (Baltimore, Md.)2010
Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion.
Article in Hepatology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- The prognostic value of vessels encapsulating tumor clusters (VETC) in patients with hepatocellular carcinoma: a systematic review and meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Pooled it
- Sox2 expression predicts poor survival of hepatocellular carcinoma patients and it promotes liver cancer cell invasion by activating Slug.Medical oncology (Northwood, London, England) · 2013Trial
- Schisandrin B attenuates cancer invasion and metastasis via inhibiting epithelial-mesenchymal transition.PloS one · 2012Trial
- Tumor-associated macrophages in hepatocellular carcinoma: Cellular plasticity and therapy resistance in crosstalk.Journal of pharmaceutical analysis · 2026Review
- An Interpretable MRI-Based Machine Learning Model for Preoperative Identification of the Vascular Dissemination Phenotype in Hepatocellular Carcinoma: A Dual-Center Study.Journal of hepatocellular carcinoma · 2026Article
- The PI3K/Akt/mTOR Pathway: Immuno-Metabolic Orchestration in IR/MASH-Associated Hepatocellular Carcinoma.International journal of biological sciences · 2025Review
- Melatonin enhances the efficacy of anti-PD-L1 by improving hypoxia in residual tumors after insufficient radiofrequency ablation.Journal of pharmaceutical analysis · 2024Article
- Clinical significance of PNO1 as a novel biomarker and therapeutic target of hepatocellular carcinoma.Journal of cellular and molecular medicine · 2024Article
- Review
- Tacrolimus induces fibroblast-to-myofibroblast transition via a TGF-β-dependent mechanism to contribute to renal fibrosis.American journal of physiology. Renal physiology · 2023Article
- CRISPR activation screening in a mouse model for drivers of hepatocellular carcinoma growth and metastasis.iScience · 2023Article
- Small Molecule Inhibitors for Hepatocellular Carcinoma: Advances and Challenges.Molecules (Basel, Switzerland) · 2022Review
- KIF3A inhibits nasopharyngeal carcinoma proliferation, migration and invasion by interacting with β-catenin to suppress its nuclear accumulation.American journal of cancer research · 2022Article
- Development of a novel Bruton's tyrosine kinase inhibitor that exerts anti-cancer activities potentiates response of chemotherapeutic agents in multiple myeloma stem cell-like cells.Frontiers in pharmacology · 2022Article
- Advances in Liver Cancer Stem Cell Isolation and their Characterization.Stem cell reviews and reports · 2021Review
- Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle-Do Myokines Play a Role?Antioxidants (Basel, Switzerland) · 2021Review
- Impact of gestational low-protein intake on embryonic kidney microRNA expression and in nephron progenitor cells of the male fetus.PloS one · 2021Article
- Loss of ARF/INK4A Promotes Liver Progenitor Cell Transformation Toward Tumorigenicity Supporting Their Role in Hepatocarcinogenesis.Gene expression · 2020Article
- The Function of the HGF/c-Met Axis in Hepatocellular Carcinoma.Frontiers in cell and developmental biology · 2020Review
- A Newly Established Murine Cell Line as a Model for Hepatocellular Cancer in Non-Alcoholic Steatohepatitis.International journal of molecular sciences · 2019Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledEpithelial-to-mesenchymal transition (EMT) is predicted to play a critical role in metastatic disease in hepatocellular carcinoma. In this study, we used a novel murine model of EMT to elucidate a mechanism of tumor progression and metastasis. A total of 2 x 10(6) liver cells isolated from Pten(loxp/loxp)/Alb-Cre(+) mice, expanded from a single CD133(+)CD45(-) cell clone, passage 0 (P0), were sequentially transplanted to obtain two passages of tumor cells, P1 and P2. Cells were analyzed for gene expression using microarray and real-time polymerase chain reaction. Functional analysis included cell proliferation, migration, and invasion in vitro and orthotopic tumor metastasis assays in vivo. Although P0, P1, and P2 each formed tumors consistent with mixed liver epithelium, within the P2 cells, two distinct cell types were clearly visible: cells with epithelial morphology similar to P0 cells and cells with fibroblastoid morphology. These P2 mesenchymal cells demonstrated increased locomotion on wound healing; increased cell invasion on Matrigel basement membrane; increased EMT-associated gene expression of Snail1, Zeb1, and Zeb2; and down-regulated E-cadherin. P2 mesenchymal cells demonstrated significantly faster tumor growth in vivo compared with P2 epithelial counterparts, with invasion of intestine, pancreas, spleen, and lymph nodes. Furthermore, P2 mesenchymal cells secreted high levels of hepatocyte growth factor (HGF), which we propose acts in a paracrine fashion to drive epithelial cells to undergo EMT. In addition, a second murine liver cancer stem cell line with methionine adenosyltransferase 1a deficiency acquired EMT after sequential transplantations, indicating that EMT was not restricted to Pten-deleted tumors.
conclusionEMT is associated with a high rate of liver tumor proliferation, invasion, and metastasis in vivo, which is driven by HGF secreted from mesenchymal tumor cells in a feed-forward mechanism.
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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.