ArticleOncogene2016
Upregulation of the oncoprotein SET determines poor clinical outcomes in hepatocellular carcinoma and shows therapeutic potential.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- Targeting SET to counteract Lyn activation demonstrates anti-cancer potential in diffuse large B-cell lymphoma.Clinical and experimental medicine · 2025Article
- The oncoprotein SET promotes serine-derived one-carbon metabolism by regulating SHMT2 enzymatic activity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The next decade of SET: from an oncoprotein to beyond.Journal of molecular cell biology · 2024Review
- Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis.Nature communications · 2024Article
- Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis.Frontiers in immunology · 2024Review
- Targeting Protein Phosphatases for the Treatment of Chronic Liver Disease.Current drug targets · 2024Review
- Cancer progression by the okadaic acid class of tumor promoters and endogenous protein inhibitors of PP2A, SET and CIP2A.Journal of cancer research and clinical oncology · 2023Review
- A Novel Mouse Model of Combined Hepatocellular-Cholangiocarcinoma Induced by Diethylnitrosamine and Loss ofCancers · 2023Article
- Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population.BMC genomics · 2023Article
- The E3 Ligase TRIM4 Facilitates SET Ubiquitin-Mediated Degradation to Enhance ER-α Action in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer.BMC cancer · 2021Article
- Bi-Functional Peptides as a New Therapeutic Tool for Hepatocellular Carcinoma.Pharmaceutics · 2021Article
- Template activating factor-I epigenetically regulates the TERT transcription in human cancer cells.Scientific reports · 2021Article
- Molecular mechanisms of circular RNAs, transforming growth factor-β, and long noncoding RNAs in hepatocellular carcinoma.Cancer medicine · 2019Review
- Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression.Redox biology · 2019Review
- Canagliflozin inhibits growth of hepatocellular carcinoma via blocking glucose-influx-induced β-catenin activation.Cell death & disease · 2019Article
- Cyclin-dependent kinase 1-mediated phosphorylation of SET at serine 7 is essential for its oncogenic activity.Cell death & disease · 2019Article
- Deregulation of SET is Associated with Tumor Progression and Predicts Adverse Outcome in Patients with Early-Stage Colorectal Cancer.Journal of clinical medicine · 2019Article
- Targeting SET to restore PP2A activity disrupts an oncogenic CIP2A-feedforward loop and impairs triple negative breast cancer progression.EBioMedicine · 2019Article
- Circular RNAs: Characteristics, Function and Clinical Significance in Hepatocellular Carcinoma.Cancers · 2018Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The SET protein is a potent inhibitor of protein phosphatase 2A (PP2A). Here, we report the oncogenic role of SET in hepatocarcinogenesis, clinical aggressiveness and anti-hepatocellular carcinoma (HCC) therapeutics. By analyzing samples obtained from 147 HCC patients, we found that SET overexpression was detected specifically in 30.6% HCC tumor samples, and was significantly associated with worse clinical features and high p-Akt expression in HCC tumors. Co-expression of SET and Akt predicted shorter post-operative recurrence-free survival in this cohort (P=0.045). Furthermore, SET was significantly associated with cell growth and hepatosphere formation. To elucidate the anti-HCC potential of targeting SET, we generated a novel SET antagonist, EMQA (N(4)-(3-ethynylphenyl)-6,7-dimethoxy-N(2)-(4-phenoxyphenyl) quinazoline-2,4-diamine). EMQA enhanced PP2A activity via disrupting SET-PP2Ac (catalytic domain of PP2A) binding in HCC cells, which restored PP2A-mediated p-Akt downregulation and promoted HCC cell death. In HCC cells or recombinant proteins expressing the N- and C- truncated forms of SET, only the C-terminal SET was required for EMQA targeting. Furthermore, combining sorafenib and EMQA showed good synergism in inhibiting HCC survival. Our findings suggested the oncogenic role of SET and the adverse prognostic value of SET overexpression in HCC. This alteration defines a subgroup of HCC patients who could benefit from SET antagonists, such as EMQA.
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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.