DCAF1 interacts with PARD3 to promote hepatocellular carcinoma progression and metastasis by activating the Akt signaling pathway.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 8308647 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-9966 (Electronic) Linking ISSN: 03929078 NLM ISO Abbreviation: J Exp Clin Cancer Res Subsets: MEDLINE
    • Publication Information:
      Publication: 2009- : London : BioMed Central
      Original Publication: [Roma] : APSIT,
    • Subject Terms:
      Carcinoma, Hepatocellular*/metabolism ; Carcinoma, Hepatocellular*/pathology ; Carcinoma, Hepatocellular*/genetics ; Disease Progression* ; Liver Neoplasms*/metabolism ; Liver Neoplasms*/pathology ; Liver Neoplasms*/genetics ; Neoplasm Metastasis* ; Proto-Oncogene Proteins c-akt*/metabolism ; Signal Transduction*; Animals ; Female ; Humans ; Male ; Mice ; Adaptor Proteins, Signal Transducing/metabolism ; Adaptor Proteins, Signal Transducing/genetics ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Prognosis ; Xenograft Model Antitumor Assays
    • Abstract:
      Background: Hepatocellular carcinoma (HCC) is a fatal malignancy with poor prognosis due to lack of effective clinical interference. DCAF1 plays a vital role in regulating cell growth and proliferation, and is involved in the progression of various malignancies. However, the function of DCAF1 in HCC development and the underlying mechanism are still unknown. This study aimed to explore the effect of DCAF1 in HCC and the corresponding molecular mechanism.
      Methods: Quantitative real-time PCR, Western blot and immunostaining were used to determine DCAF1 expression in tumor tissues and cell lines. Subsequently, in vitro and in vivo experiments were conducted to explore the function of DCAF1 in tumor growth and metastasis in HCC. Coimmunoprecipitation, mass spectrometry and RNA sequencing were performed to identify the underlying molecular mechanisms.
      Results: In this study, we found that DCAF1 was observably upregulated and associated with poor prognosis in HCC. Knockdown of DCAF1 inhibited tumor proliferation and metastasis and promoted tumor apoptosis, whereas overexpressing DCAF1 yielded opposite effects. Mechanistically, DCAF1 could activate the Akt signaling pathway by binding to PARD3 and enhancing its expression. We also found that the combined application of DCAF1 knockdown and Akt inhibitor could significantly suppress subcutaneous xenograft tumor growth.
      Conclusions: Our study illustrates that DCAF1 plays a crucial role in HCC development and the DCAF1/PARD3/Akt axis presents a potentially effective therapeutic strategy for HCC.
      (© 2024. The Author(s).)
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    • Grant Information:
      81930086 the State Key Program of National Natural Science Foundation; 82120108012 the State Key Program of National Natural Science Foundation; 202204295107020008 the Key Research and Development Program of AnHui Province; 2022AH010070 the Program of Department of Education of Anhui Province
    • Contributed Indexing:
      Keywords: Akt; DCAF1; Hepatocellular carcinoma; PARD3
    • Accession Number:
      0 (Adaptor Proteins, Signal Transducing)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
      0 (PARD3 protein, human)
      EC 2.7.11.1 (DCAF1 protein, human)
    • Publication Date:
      Date Created: 20240506 Date Completed: 20240507 Latest Revision: 20240523
    • Publication Date:
      20240523
    • Accession Number:
      PMC11071249
    • Accession Number:
      10.1186/s13046-024-03055-2
    • Accession Number:
      38711082