ArticleAnnals of translational medicine2020
Cimetidine promotes STUB1-mediated degradation of tumoral FOXP3 by activating PI3K-Akt pathway in gastric cancer.
Article in Annals of translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 10 citations in OpenAlex.
- Article
- Regulatory T Cells in Autoimmune Vasculitis.Frontiers in immunology · 2022Review
- A new candidate oncogenic lncRNA derived from pseudogene WFDC21P promotes tumor progression in gastric cancer.Cell death & disease · 2021Article
- Tripartite motif-containing protein 6 facilitates growth and migration of breast cancer through degradation of STUB1.European journal of histochemistry : EJH · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrevious studies have confirmed the antitumor effects of cimetidine, while the therapeutic targets and the mechanisms are not yet fully understood. We previously reported the protumoral role of endogenous FOXP3 in gastric cancer (GC), but whether cimetidine plays an antitumor role by targeting FOXP3 is still unknown.
methodsA series of assays were used to examine the role of cimetidine on the malignant behaviors and the expression of endogenous FOXP3 in GC cells. The role of cimetidine on ligase E3-STUB1and the role of STUB1 on FOXP3 level were examined, with the signaling pathway involved in these processes also being explored.
resultsCimetidine inhibited the malignant behaviors of GC cells, and led to the ubiquitination/degradation of FOXP3. Moreover, cimetidine promoted STUB1 expression, STUB1 knockdown rescued the decline of FOXP3 in cimetidine-treated GC cells, and reduced the turnover effect of cimetidine on GC cells, but had minimal effect in untreated cells. Immunoprecipitation (IP) assay confirmed the formation of the STUB1-FOXP3 complex in cimetidine-treated GC cells. Furthermore, Cimetidine promoted STUB1 expression by activating PI3K/Akt pathway, and the inhibition of PI3K/Akt pathway rescued the decline of FOXP3 by suppressing the upregulation of STUB1.
conclusionsCimetidine suppressed GC development by promoting STUB1-mediated ubiquitination/degradation of endogenous FOXP3 through the activation of the PI3K/Akt pathway.
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