ArticleOncogene2003
Distortion of autocrine transforming growth factor beta signal accelerates malignant potential by enhancing cell growth as well as PAI-1 and VEGF production in human hepatocellular carcinoma cells.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 43 citations in OpenAlex.
- Mixed cryoglobulinemia decelerates hepatocellular carcinoma development in hepatitis C patients with SVR by downregulating regulatory B cells: a 12-year prospective cohort study.Oncoimmunology · 2025Article
- Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis.Frontiers in immunology · 2024Review
- Review
- Autocrine TGF-β in Cancer: Review of the Literature and Caveats in Experimental Analysis.International journal of molecular sciences · 2021Review
- Review
- FOXP3 inhibits angiogenesis by downregulating VEGF in breast cancer.Cell death & disease · 2018Article
- TGF-β signal shifting between tumor suppression and fibro-carcinogenesis in human chronic liver diseases.Journal of gastroenterology · 2014Review
- Transforming growth factor-β signaling in hepatocytes promotes hepatic fibrosis and carcinogenesis in mice with hepatocyte-specific deletion of TAK1.Gastroenterology · 2013Article
- Smad phosphoisoform signals in acute and chronic liver injury: similarities and differences between epithelial and mesenchymal cells.Cell and tissue research · 2012Review
- Opposite functions of HIF-α isoforms in VEGF induction by TGF-β1 under non-hypoxic conditions.Oncogene · 2011Article
- Regulation of TGF-β1-Induced Pro-Apoptotic Signaling by Growth Factor Receptors and Extracellular Matrix Receptor Integrins in the Liver.Frontiers in physiology · 2011Article
- Multimodality imaging of TGFbeta signaling in breast cancer metastases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2009Article
- Investigation of immunosuppressive mechanisms in a mouse glioma model.Journal of neuro-oncology · 2009Article
- MicroRNA involvement in hepatocellular carcinoma.Journal of cellular and molecular medicine · 2008Review
- Systems biology of vascular endothelial growth factors.Microcirculation (New York, N.Y. : 1994) · 2008Review
- Correlation analysis of liver tumor-associated genes with liver regeneration.World journal of gastroenterology · 2007Article
- Crk-associated substrate lymphocyte type regulates transforming growth factor-beta signaling by inhibiting Smad6 and Smad7.Oncogene · 2007Article
- Role of transforming growth factor-beta1-smad signal transduction pathway in patients with hepatocellular carcinoma.World journal of gastroenterology · 2006Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to growth inhibitory effects of transforming growth factor (TGF)-beta is a frequent consequence of malignant transformation. On the other hand, serum concentrations of TGF-beta, plasminogen activator inhibitor type 1 (PAI-1), and vascular endothelial growth factor (VEGF) are elevated as tumor progresses. The molecular mechanism of autocrine TGF-beta signaling and its effects on PAI-1 and VEGF production in human hepatocellular carcinoma (HCC) is unknown. TGF-beta signaling involves TGF-beta type I receptor-mediated phosphorylation of serine residues within the conserved SSXS motif at the C-terminus of Smad2 and Smad3. To investigate the involvement of autocrine TGF-beta signal in cell growth, PAI-1 and VEGF production of HCC, we made stable transfectants of human HCC line (HuH-7 cells) to express a mutant Smad2(3S-A), in which serine residues of SSXS motif were changed to alanine. The transfectants demonstrated an impaired Smad2 signaling. Along with the resistance to growth inhibition by TGF-beta, forced expression of Smad2(3S-A) induced endogenous TGF-beta secretion. Moreover, this increased TGF-beta enhanced ligand-dependent signaling through the activated Smad3 and Smad4 complex, and transcriptional activities of PAI-1 and VEGF genes. In conclusion, distortion of autocrine TGF-beta signals in human HCC accelerates their malignant potential by enhancing cell growth as well as PAI-1 and VEGF production.
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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.