ArticleHepatology (Baltimore, Md.)2015
βII-Spectrin (SPTBN1) suppresses progression of hepatocellular carcinoma and Wnt signaling by regulation of Wnt inhibitor kallistatin.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 95 citations in OpenAlex.
- Article
- Novel role of the class II α-isoform of phosphatidylinositol 3-kinase in hepatocellular carcinoma: suppressing metastasis by targeting Wnt/β-catenin signaling via inhibiting phosphorylation of LRP6.Cancer cell international · 2026Article
- Mechanistic study of miR‑369‑3p in regulating the Wnt/β‑catenin signaling pathway via targeting SPTBN1 in inflammatory response and bone destruction of rheumatoid arthritis.Molecular medicine reports · 2026Article
- Gentamicin and Citronella-Derived Compounds as Dual Modulators of Inflammation-Associated Targets in Acne Vulgaris.International journal of molecular sciences · 2025Article
- A Novel tRF, HCETSR, Derived From tRNA-Glu/TTC, Inhibits HCC Malignancy by Regulating the SPBTN1-catenin Complex Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Aldehydes alter TGF-β signaling and induce obesity and cancer.Cell reports · 2024Article
- WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities.Genes & diseases · 2024Review
- Article
- SPTBN1 Mediates the Cytoplasmic Constraint of PTTG1, Impairing Its Oncogenic Activity in Human Seminoma.International journal of molecular sciences · 2023Article
- Multidimensional outlook on the pathophysiology of cervical cancer invasion and metastasis.Molecular and cellular biochemistry · 2023Review
- A positive feedback circuit between RN7SK snRNA and mMolecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Article
- Genetic heterogeneity of liver cancer stem cells.Anatomy & cell biology · 2023Article
- SPTBN1 abrogates renal clear cell carcinoma progression via glycolysis reprogramming in a GPT2-dependent manner.Journal of translational medicine · 2022Article
- Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside.Experimental hematology & oncology · 2022Review
- Different responses to risperidone treatment in Schizophrenia: a multicenter genome-wide association and whole exome sequencing joint study.Translational psychiatry · 2022Article
- The Smad4-MYO18A-PP1A complex regulates β-catenin phosphorylation and pemigatinib resistance by inhibiting PAK1 in cholangiocarcinoma.Cell death and differentiation · 2022Article
- Long non-coding RNAs as the critical regulators of epithelial mesenchymal transition in colorectal tumor cells: an overview.Cancer cell international · 2022Review
- Prognostic implications of NScientific reports · 2022Article
- Loss of SPTBN1 Suppresses Autophagy Via SETD7-mediated YAP Methylation in Hepatocellular Carcinoma Initiation and Development.Cellular and molecular gastroenterology and hepatology · 2022Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledβII-Spectrin (SPTBN1) is an adapter protein for Smad3/Smad4 complex formation during transforming growth factor beta (TGF-β) signal transduction. Forty percent of SPTBN1(+/-) mice spontaneously develop hepatocellular carcinoma (HCC), and most cases of human HCC have significant reductions in SPTBN1 expression. In this study, we investigated the possible mechanisms by which loss of SPTBN1 may contribute to tumorigenesis. Livers of SPTBN1(+/-) mice, compared to wild-type mouse livers, display a significant increase in epithelial cell adhesion molecule-positive (EpCAM(+)) cells and overall EpCAM expression. Inhibition of SPTBN1 in human HCC cell lines increased the expression of stem cell markers EpCAM, Claudin7, and Oct4, as well as decreased E-cadherin expression and increased expression of vimentin and c-Myc, suggesting reversion of these cells to a less differentiated state. HCC cells with decreased SPTBN1 also demonstrate increased sphere formation, xenograft tumor development, and invasion. Here we investigate possible mechanisms by which SPTBN1 may influence the stem cell traits and aggressive behavior of HCC cell lines. We found that HCC cells with decreased SPTBN1 express much less of the Wnt inhibitor kallistatin and exhibit decreased β-catenin phosphorylation and increased β-catenin nuclear localization, indicating Wnt signaling activation. Restoration of kallistatin expression in these cells reversed the observed Wnt activation.
conclusionSPTBN1 expression in human HCC tissues is positively correlated with E-cadherin and kallistatin levels, and decreased SPTBN1 and kallistatin gene expression is associated with decreased relapse-free survival. Our data suggest that loss of SPTBN1 activates Wnt signaling, which promotes acquisition of stem cell-like features, and ultimately contributes to malignant tumor progression.
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