DEPTOR as a novel prognostic marker inhibits the proliferation via deactivating mTOR signaling pathway in gastric cancer cells.

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  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 0373226 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2422 (Electronic) Linking ISSN: 00144827 NLM ISO Abbreviation: Exp Cell Res Subsets: MEDLINE
    • Publication Information:
      Publication: Orlando Fl : Academic Press
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Stomach Neoplasms*/genetics; Humans ; Prognosis ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Cell Line, Tumor
    • Abstract:
      Aberrantly activated mTOR signaling pathway is commonly found in malignancies including gastric cancer (GC). DEPTOR, as a naturally occurred inhibitor of mTOR, functions in the pro- or anti-tumor manner depending on distinct tumor contexts. However, the roles of DEPTOR in GC remain largely unknown. In this study, DEPTOR expression was identified to be significantly decreased in GC tissues compared with matched normal gastric tissues, and reduced DEPTOR level was indicative of poor prognosis in patients. Restored DEPTOR expression inhibited the propagation in AGS and NCI-N87 cells, whose DEPTOR levels are low, via deactivating mTOR signaling pathway. Likewise, cabergoline (CAB) attenuated the proliferation in AGS and NCI-N87 cells via partially rescuing DEPTOR protein level. Targeted metabolomics analysis showed that several key metabolites, such as l-serine, significantly changed in AGS cells with DEPTOR restoration. These results revealed the anti-proliferation function of DEPTOR in GC cells, suggesting that restored DEPTOR expression using CAB may be a potential therapeutic approach for patients with GC.
      Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2023. Published by Elsevier Inc.)
    • Contributed Indexing:
      Keywords: Cabergoline; DEPTOR; Gastric cancer; Proliferation; mTOR
    • Accession Number:
      0 (Intracellular Signaling Peptides and Proteins)
      EC 2.7.11.1 (TOR Serine-Threonine Kinases)
      EC 2.7.1.1 (MTOR protein, human)
      EC 2.7.1.1 (DEPTOR protein, human)
    • Publication Date:
      Date Created: 20230413 Date Completed: 20230427 Latest Revision: 20230501
    • Publication Date:
      20230501
    • Accession Number:
      10.1016/j.yexcr.2023.113598
    • Accession Number:
      37054772