ArticleOncogene2015
TGF-β signaling alters the pattern of liver tumorigenesis induced by Pten inactivation.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Developing a strain-dependent susceptibility to hepatocellular carcinoma in a murine model based on histopathological evidence and genetic context.Animal models and experimental medicine · 2026Article
- Withaferin A inhibits proliferation of human endometrial cancer cells via transforming growth factor-β (TGF-β) signalling.3 Biotech · 2021Article
- Review
- Identification of miR-135b as a novel regulator of TGFβ pathway in gastric cancer.Journal of physiology and biochemistry · 2020Article
- Long-TermMicroorganisms · 2020Article
- A Transforming Growth Factor-β and H19 Signaling Axis in Tumor-Initiating Hepatocytes That Regulates Hepatic Carcinogenesis.Hepatology (Baltimore, Md.) · 2019Article
- Screen for reactivation of MeCP2 on the inactive X chromosome identifies the BMP/TGF-β superfamily as a regulator of XIST expression.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Identification of miR-101-3p targets and functional features based on bioinformatics, meta-analysis and experimental verification in hepatocellular carcinoma.American journal of translational research · 2017Article
- Epithelial Transforming Growth Factor-β Signaling Does Not Contribute to Liver Fibrosis but Protects Mice From Cholangiocarcinoma.Gastroenterology · 2016Article
- Hepatic stellate cells: central modulators of hepatic carcinogenesis.BMC gastroenterology · 2015Review
- MicroRNA-3127 promotes cell proliferation and tumorigenicity in hepatocellular carcinoma by disrupting of PI3K/AKT negative regulation.Oncotarget · 2015Article
- Turning hepatic cancer stem cells inside out--a deeper understanding through multiple perspectives.Molecules and cells · 2015Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatocarcinogenesis results from the accumulation of genetic and epigenetic changes in liver cells. A common mechanism through which these alterations induce liver cancer is by deregulating signaling pathways. A number of signaling pathways, including the PI3K/PTEN/AKT and transforming growth factor β (TGF-β) pathways have been implicated in normal liver development as well as in cancer formation. In this study, we assessed the effect of the TGF-β signaling pathway on liver tumors induced by phosphatase and tensin homolog (Pten) loss. Inactivation of only the TGF-β receptor type II, Tgfbr2, in the mouse liver (Tgfbr2(LKO)) had no overt phenotype, while inactivation of Pten alone (Pten(LKO)), resulted in the formation of both hepatocellular carcinomas and cholangiocarcinomas (CC). Interestingly, deletion of both Pten and Tgfbr2 (Pten(LKO);Tgfbr2(LKO)) in the mouse liver resulted in a dramatic shift in tumor type to predominantly CC. Assessment of the PI3K/PTEN/AKT pathway revealed increased phosphorylation of AKT and glycogen synthase kinase 3 beta (GSK-3β) in both the Pten(LKO) and Pten(LKO);Tgfbr2(LKO) mice, suggesting that this pathway is constitutively active regardless of the status of the TGF-β signaling pathway. However, phosphorylation of p70 S6 kinase was observed in the liver of all three phenotypes (Tgfbr2(LKO), Pten(LKO), Pten(LKO);Tgfbr2(LKO)) indicating that the loss of Tgfbr2 and/or Pten leads to an increase in this signaling pathway. Analysis of markers of liver progenitor/stem cells revealed that the loss of TGF-β signaling resulted in increased expression of c-Kit and CD133. Furthermore, in addition to increased c-Kit and CD133, Scf and EpCam expression were also increased in the double knock-out mice. These results suggest that the alteration in tumor types between the Pten(LKO) mice and Pten(LKO);Tgfbr2(LKO) mice is secondary to the altered regulation of stem-cell features induced by the loss of TGF-β signaling.
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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.