ArticlePloS one2013
TGF-β signaling is often attenuated during hepatotumorigenesis, but is retained for the malignancy of hepatocellular carcinoma cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 26 citations in OpenAlex.
- Oncogenic role of PMEPA1 and its association with immune exhaustion and TGF-β activation in HCC.JHEP reports : innovation in hepatology · 2024Article
- Article
- Review
- Imbalance of TGF-β1/BMP-7 pathways induced by M2-polarized macrophages promotes hepatocellular carcinoma aggressiveness.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Distinct functions of transforming growth factor-β signaling in c-MYC driven hepatocellular carcinoma initiation and progression.Cell death & disease · 2021Article
- MiRNA-target network analysis identifies potential biomarkers for Traditional Chinese Medicine (TCM) syndrome development evaluation in hepatitis B caused liver cirrhosis.Scientific reports · 2017Article
- The SMAD2/3 pathway is involved in hepaCAM-induced apoptosis by inhibiting the nuclear translocation of SMAD2/3 in bladder cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Transcriptional Profiling and miRNA-Target Network Analysis Identify Potential Biomarkers for Efficacy Evaluation of Fuzheng-Huayu Formula-Treated Hepatitis B Caused Liver Cirrhosis.International journal of molecular sciences · 2016Article
- Hepatic stellate cells: central modulators of hepatic carcinogenesis.BMC gastroenterology · 2015Review
- Novel regulation of Ski protein stability and endosomal sorting by actin cytoskeleton dynamics in hepatocytes.The Journal of biological chemistry · 2015Article
- Dynamical Regulation Analysis Identifies Molecular Mechanisms of Fuzheng-Huayu Formula against Hepatitis B-Caused Liver Cirrhosis.Evidence-based complementary and alternative medicine : eCAM · 2015Article
- A TALEN-based specific transcript knock-down of PIWIL2 suppresses cell growth in HepG2 tumor cell.Cell proliferation · 2014Article
- Smad3 phospho-isoform signaling in hepatitis C virus-related chronic liver diseases.World journal of gastroenterology · 2014Review
- Recent insights into hepatic cancer stem cells.Hepatology international · 2014Article
- TGF-β signal shifting between tumor suppression and fibro-carcinogenesis in human chronic liver diseases.Journal of gastroenterology · 2014Review
- Review
- Targeted treatment of mutatedLung Cancer (Auckland, N.Z.) · 2014Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The role of transforming growth factor-beta (TGF-β) signaling in hepatocarcinogenesis remains controversial. We aimed to reveal TGF-β signaling status in human and murine tissues of hepatocellular carcinoma (HCC) and the mechanisms that mediate TGF-β's role in regulating HCC malignancy. Here, TGF-β pathway component expression and activation in human and murine HCC tissues were measured with quantitative RT-PCR and Western blotting assays. The role of TGF-β receptor and Smad signaling in the growth and survival of several HCC cell lines was determined with several in vitro and in vivo approaches. We found that TGF-β receptor II (TβRII) expression was downregulated in two different HCC patient cohorts. Consistently, Smad3 phosphorylation was also downregulated in HCC tissues in comparison to that in adjacent normal tissues. Interestingly, many HCC cell lines were sensitive to TGF-β and growth-inhibited by exogenous TGF-β. However, stable knockdown of TβRII inhibited cell growth on plastic and in soft agar, and induced apoptosis resulting in suppressed subcutaneous tumor growth and metastatic potential in vivo. Furthermore, knockdown of Smad4 also led to a significant inhibition of growth on plastic and in soft agar with concomitant increase of apoptosis, PTEN expression, and reduced nuclear accumulation of linker region-phosphorylated Smad3. Taken together, TGF-β signaling pathway plays a dichotomous role in hepatocellular carcinogenesis. It appears to suppress HCC development, but is retained for HCC cell survival and malignancy. Furthermore, Smad4 can mediate both growth inhibitory activity induced by exogenous TGF-β and the survival activity induced by autocrine TGF-β revealing a delicate selection of the two opposing activities of TGF-β during HCC evolution.
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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.