ArticleOncogene2021
β-Trcp and CK1δ-mediated degradation of LZTS2 activates PI3K/AKT signaling to drive tumorigenesis and metastasis in hepatocellular carcinoma.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- LZTS2 Negatively Regulates Centrosomal CEP135 Levels and Microtubule Nucleation.Cytoskeleton (Hoboken, N.J.) · 2026Article
- The role of SH3RF2 in lung squamous cell carcinoma and M2 polarization: insights into LZTS2 ubiquitination.Biology direct · 2025Article
- Disrupting CCDC137-mediated LZTS2 and β-TrCP interaction in the nucleus inhibits hepatocellular carcinoma development via β-catenin and AKT.Cell death and differentiation · 2025Article
- WDR20 prevents hepatocellular carcinoma senescence by orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Strategic advancement of E3 ubiquitin ligase in the management of hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2024Review
- USP9X-mediated REV1 deubiquitination promotes lung cancer radioresistance via the action of REV1 as a Rad18 molecular scaffold for cystathionine γ-lyase.Journal of biomedical science · 2024Article
- Annexin A2 combined with TTK accelerates esophageal cancer progression via the Akt/mTOR signaling pathway.Cell death & disease · 2024Article
- Decidual stromal cells-derived exosomes incurred insufficient migration and invasion of trophoblast by disturbing of β-TrCP-mediated snail ubiquitination and degradation in unexplained recurrent spontaneous abortion.European journal of medical research · 2024Article
- The Antitumor and Sorafenib-resistant Reversal Effects of Ursolic Acid on Hepatocellular Carcinoma via Targeting ING5.International journal of biological sciences · 2024Article
- E3 ubiquitin ligases in nasopharyngeal carcinoma and implications for therapies.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Degradation of helicase-like transcription factor (HLTF) by β-TrCP promotes hepatocarcinogenesis via activation of the p62/mTOR axis.Journal of molecular cell biology · 2023Article
- FIBP interacts with transcription factor STAT3 to induce EME1 expression and drive radioresistance in lung adenocarcinoma.International journal of biological sciences · 2023Article
- FBXO43 increases CCND1 stability to promote hepatocellular carcinoma cell proliferation and migration.Frontiers in oncology · 2023Article
- New insights into fibrotic signaling in hepatocellular carcinoma.Frontiers in oncology · 2023Review
- Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma.Biomedicines · 2022Review
- Activation of the β‑TrCP/IκBα/inflammation axis limits the sensitivity of liver cancer cells to neddylation inhibition.Oncology reports · 2022Article
- lncRNA XLOC013218 promotes cell proliferation and TMZ resistance by targeting the PIK3R2-mediated PI3K/AKT pathway in glioma.Cancer science · 2022Article
- Circulating microRNAs (miR-16, miR-22, miR-122) expression and early diagnosis of hepatocellular carcinoma.Journal of clinical laboratory analysis · 2022Article
- Targeting KDM4C enhances CD8Journal for immunotherapy of cancer · 2022Article
Corrections and comments
- Retracted
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Distant metastasis is the leading cause of treatment failure in patients with hepatocellular carcinoma (HCC). However, the underlying mechanisms have not been fully elucidated. Here, we report that Leucine zipper tumor suppressor 2 (LZTS2) is downregulated and correlated with poor prognosis in HCC. Furthermore, we provide evidence that LZTS2 associates with p85 to inhibit the activation of PI3K/AKT signaling and impairs HCC tumorigenesis and metastasis in vitro and in vivo. Moreover, we identify LZTS2 as a bona fide substrate of the E3 ligase β-Trcp and protein kinase CK1δ, which are responsible for the ubiquitination and degradation of LZTS2. Importantly, we show that the β-Trcp and CK1δ-mediated degradation of LZTS2 promotes HCC progression and metastasis by activating PI3K/AKT signaling. Collectively, our study not only illustrates the roles of LZTS2 in regulating HCC tumorigenesis and metastasis but also reveals a novel posttranslational modification of LZTS2 by β-Trcp and CK1δ, indicating that the β-Trcp/CK1δ/LZTS2/PI3K axis may be a novel oncogenic driver involved in HCC progression and metastasis.
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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 Socratic graph.