ArticleThe Journal of clinical investigation2016
TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- New insights into biomarkers and risk stratification to predict hepatocellular cancer.Molecular medicine (Cambridge, Mass.) · 2025Review
- Aldehydes alter TGF-β signaling and induce obesity and cancer.Cell reports · 2024Article
- Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis.Genes & cancer · 2024Article
- SPTBN1 Mediates the Cytoplasmic Constraint of PTTG1, Impairing Its Oncogenic Activity in Human Seminoma.International journal of molecular sciences · 2023Article
- Interactions between the DNA Damage Response and the Telomere Complex in Carcinogenesis: A Hypothesis.Current issues in molecular biology · 2023Review
- Role of PDLIM1 in hepatic stellate cell activation and liver fibrosis progression.Scientific reports · 2023Article
- E3 ubiquitin ligases in cancer stem cells: key regulators of cancer hallmarks and novel therapeutic opportunities.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- DNA architectural protein CTCF facilitates subset-specific chromatin interactions to limit the formation of memory CD8Immunity · 2023Article
- Article
- Impaired reciprocal regulation between SIRT6 and TGF-β signaling in fatty liver.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Loss of SPTBN1 Suppresses Autophagy Via SETD7-mediated YAP Methylation in Hepatocellular Carcinoma Initiation and Development.Cellular and molecular gastroenterology and hepatology · 2022Article
- Pathogenesis to management of hepatocellular carcinoma.Genes & cancer · 2022Review
- β2-spectrin (SPTBN1) as a therapeutic target for diet-induced liver disease and preventing cancer development.Science translational medicine · 2021Article
- The telomere complex and the origin of the cancer stem cell.Biomarker research · 2021Review
- Heterozygous variants in SPTBN1 cause intellectual disability and autism.American journal of medical genetics. Part A · 2021Article
- Article
- βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases.International journal of biological sciences · 2021Review
- Article
- Targeting the E3 Ubiquitin Ligase PJA1 Enhances Tumor-Suppressing TGFβ Signaling.Cancer research · 2020Article
- TGF-β1 accelerates the hepatitis B virus X-induced malignant transformation of hepatic progenitor cells by upregulating miR-199a-3p.Oncogene · 2020Article
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Authors and funding
30 authors at 9 institutions in 3 countries.
Funding
Abstract
Beckwith-Wiedemann syndrome (BWS) is a human stem cell disorder, and individuals with this disease have a substantially increased risk (~800-fold) of developing tumors. Epigenetic silencing of β2-spectrin (β2SP, encoded by SPTBN1), a SMAD adaptor for TGF-β signaling, is causally associated with BWS; however, a role of TGF-β deficiency in BWS-associated neoplastic transformation is unexplored. Here, we have reported that double-heterozygous Sptbn1+/- Smad3+/- mice, which have defective TGF-β signaling, develop multiple tumors that are phenotypically similar to those of BWS patients. Moreover, tumorigenesis-associated genes IGF2 and telomerase reverse transcriptase (TERT) were overexpressed in fibroblasts from BWS patients and TGF-β-defective mice. We further determined that chromatin insulator CCCTC-binding factor (CTCF) is TGF-β inducible and facilitates TGF-β-mediated repression of TERT transcription via interactions with β2SP and SMAD3. This regulation was abrogated in TGF-β-defective mice and BWS, resulting in TERT overexpression. Imprinting of the IGF2/H19 locus and the CDKN1C/KCNQ1 locus on chromosome 11p15.5 is mediated by CTCF, and this regulation is lost in BWS, leading to aberrant overexpression of growth-promoting genes. Therefore, we propose that loss of CTCF-dependent imprinting of tumor-promoting genes, such as IGF2 and TERT, results from a defective TGF-β pathway and is responsible at least in part for BWS-associated tumorigenesis as well as sporadic human cancers that are frequently associated with SPTBN1 and SMAD3 mutations.
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