ArticleHepatology (Baltimore, Md.)2011
Transforming growth factor-β adaptor, β2-spectrin, modulates cyclin dependent kinase 4 to reduce development of hepatocellular cancer.
Article in Hepatology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Computational Identification of Novel Stage-Specific Biomarkers in Colorectal Cancer Progression.PloS one · 2016Pooled it
- Transforming Growth Factor-β Signaling in Alcohol-Associated Liver Disease: A Multicellular Perspective.The American journal of pathology · 2026Review
- Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis.Genes & cancer · 2024Article
- Role of PDLIM1 in hepatic stellate cell activation and liver fibrosis progression.Scientific reports · 2023Article
- Article
- Review
- Mir-454-3p induced WTX deficiency promotes hepatocellular carcinoma progressions through regulating TGF-β signaling pathway.Journal of Cancer · 2022Article
- β2-spectrin (SPTBN1) as a therapeutic target for diet-induced liver disease and preventing cancer development.Science translational medicine · 2021Article
- β2SP/TET2 complex regulates gene 5hmC modification after cerebral ischemia.Journal of cellular and molecular medicine · 2021Article
- Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.Nature genetics · 2021Article
- MiR-362 suppresses cervical cancer progression via directly targeting BAP31 and activating TGFβ/Smad pathway.Cancer medicine · 2021Article
- Cytoskeletal Remodeling in Cancer.Biology · 2020Review
- A Fresh Look at the Structure, Regulation, and Functions of Fodrin.Molecular and cellular biology · 2020Review
- Review
- microRNA-17 functions as an oncogene by downregulating Smad3 expression in hepatocellular carcinoma.Cell death & disease · 2019Article
- A Transforming Growth Factor-β and H19 Signaling Axis in Tumor-Initiating Hepatocytes That Regulates Hepatic Carcinogenesis.Hepatology (Baltimore, Md.) · 2019Article
- A Potential Antitumor Effect of Dendritic Cells Fused with Cancer Stem Cells in Hepatocellular Carcinoma.Stem cells international · 2019Article
- αII-spectrin and βII-spectrin do not affect TGFβ1-induced myofibroblast differentiation.Cell and tissue research · 2018Article
- Transforming growth factor-β decreases side population cells in hepatocellular carcinomaOncology letters · 2018Article
- β2 spectrin-mediated differentiation repressed the properties of liver cancer stem cells through β-catenin.Cell death & disease · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
unlabelledTransforming growth factor beta (TGF-β) is an important regulator of cell growth, and loss of TGF-β signaling is a hallmark of carcinogenesis. The Smad3/4 adaptor protein β2-spectrin (β2SP) is emerging as a potent regulator of tumorigenesis through its ability to modulate the tumor suppressor function of TGF-β. However, to date the role of the TGF-β signaling pathway at specific stages of the development of hepatocellular carcinoma (HCC), particularly in relation to the activation of other oncogenic pathways, remains poorly delineated. Here we identify a mechanism by which β2SP, a crucial Smad3 adaptor, modulates cyclin dependent kinase 4 (CDK4), cell cycle progression, and suppression of HCC. Increased expression of β2SP inhibits phosphorylation of the retinoblastoma gene product (Rb) and markedly reduces CDK4 expression to a far greater extent than other CDKs and cyclins. Furthermore, suppression of CDK4 by β2SP efficiently restores Rb hypophosphorylation and cell cycle arrest in G(1) . We further demonstrate that β2SP interacts with CDK4 and Smad3 in a competitive and TGF-β-dependent manner. In addition, haploinsufficiency of cdk4 in β2sp(+/-) mice results in a dramatic decline in HCC formation compared to that observed in β2sp(+/-) mice.
conclusionβ2SP deficiency leads to CDK4 activation and contributes to dysregulation of the cell cycle, cellular proliferation, oncogene overexpression, and the formation of HCCs. Our data highlight CDK4 as an attractive target for the pharmacologic inhibition of HCC and demonstrate the importance of β2sp(+/-) mice as a model of preclinical efficacy in the treatment of HCC.
Indexed as
Identifiers
What OpenQuestion holds
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.