Clinical Significance of Combined Epithelial-Mesenchymal Transition Markers Expression and Role of Rac1 in Hepatocellular Carcinoma.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Carcinoma, Hepatocellular*/metabolism ; Liver Neoplasms*/metabolism; Humans ; Epithelial-Mesenchymal Transition/genetics ; Clinical Relevance ; Signal Transduction ; Hypoxia/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Gene Expression Regulation, Neoplastic ; rac1 GTP-Binding Protein/genetics ; rac1 GTP-Binding Protein/metabolism
    • Abstract:
      Epithelial-mesenchymal transition (EMT) has been implicated in cancer progression, invasion, and metastasis. We aimed to evaluate the correlations between clinicopathological characteristics and EMT markers in patients with hepatocellular carcinoma (HCC) who underwent surgical resection and to identify the key regulator in EMT process. Fresh-frozen HCC tissues and adjacent nontumor liver tissues from 30 patients who underwent surgical resection were provided by the Gachon University Gil Medical Center Bio Bank. Human HCC cell lines, Hep3B, SNU449, and Huh7 cells were transfected with Rac1 siRNA and exposed to hypoxic conditions. The combined EMT markers expression (down-expression of E-cadherin and overexpression of p21-activated kinases 1 (PAK1)/Snail) by Western blot in HCC tissues when compared to adjacent nontumor liver tissues was significantly associated with macrovascular invasion ( p = 0.021), microvascular invasion ( p = 0.001), large tumor size ( p = 0.021), and advanced tumor stage ( p = 0.015). Patients with combined EMT markers expression showed early recurrence and poor overall survival. In vitro studies showed that Rac1 knockdown decreased the expression of EMT markers including PAK1 and Snail in hypoxia-induced Hep3B cells and suppressed the migration and invasion of hypoxia-induced HCC cells. Rac1 may be a potential therapeutic target for inhibition of EMT process through the inhibition of PAK1 and Snail in HCC.
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    • Grant Information:
      GCU-2018-5255 Gachon University; NRF-2021R1F1A1063136 National Research Foundation of Korea
    • Contributed Indexing:
      Keywords: Rac1; Snail; epithelial-mesenchymal transition; hepatocellular carcinoma; p21-activated kinases 1
    • Accession Number:
      0 (RAC1 protein, human)
      EC 3.6.5.2 (rac1 GTP-Binding Protein)
    • Publication Date:
      Date Created: 20230121 Date Completed: 20230124 Latest Revision: 20230201
    • Publication Date:
      20231215
    • Accession Number:
      PMC9865966
    • Accession Number:
      10.3390/ijms24021765
    • Accession Number:
      36675278