PRRX1-induced epithelial-to-mesenchymal transition in salivary adenoid cystic carcinoma activates the metabolic reprogramming of free fatty acids to promote invasion and metastasis.

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  • Additional Information
    • Source:
      Publisher: Published for the Cell Kinetics Society, the European Study Group for Cell Proliferation, and the International Cell Cycle Society by Blackwell Scientific Publications Country of Publication: England NLM ID: 9105195 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2184 (Electronic) Linking ISSN: 09607722 NLM ISO Abbreviation: Cell Prolif Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Oxford, England] : Published for the Cell Kinetics Society, the European Study Group for Cell Proliferation, and the International Cell Cycle Society by Blackwell Scientific Publications, 1991-
    • Subject Terms:
      Cellular Reprogramming* ; Epithelial-Mesenchymal Transition*; Carcinoma, Adenoid Cystic/*metabolism ; Fatty Acids/*metabolism ; Homeodomain Proteins/*metabolism ; Neoplasm Proteins/*metabolism ; Salivary Gland Neoplasms/*metabolism; Animals ; Carcinoma, Adenoid Cystic/genetics ; Carcinoma, Adenoid Cystic/pathology ; Cell Line, Tumor ; Fatty Acids/genetics ; Homeodomain Proteins/genetics ; Humans ; Mice ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Proteins/genetics ; Salivary Gland Neoplasms/genetics ; Salivary Gland Neoplasms/pathology
    • Abstract:
      Objectives: Increasing evidences demonstrate a close correlation between epithelial-to-mesenchymal transition (EMT) induction and cancer lipid metabolism. However, the molecular mechanisms have not been clarified.
      Materials and Methods: In our study, the relative expression level of PRRX1 was detected, its relationship with free fatty acid (FFA) and PPARG2 was analysed in 85 SACC tissues and 15 salivary glands from the benign salivary tumours. We also compared the FFAs composition and levels in these SACC cells. PPARG2 was detected in PRRX1-induced FFAs treatment as well as Src and MMP-9 were detected in FFAs treatment-induced invasion and migration of SACC cells, and ChIP test was performed to identify the target interactions.
      Results: Our data showed that overexpression of PRRX1 induced EMT and facilitated the invasion and migration of SACC cells, and PRRX1 expression was closely associated with high FFAs level and poor prognosis of SACC patients. Furthermore, PRRX1 silence led to the increase of PPARG2 and the reduction of FFAs level and the migration and invasion of SACC cells. And inhibition of PPARG2 rescued FFAs level and migration and invasion capabilities of SACC cells. Free fatty acids treatment induced an increase of Stat5-DNA binding activity via Src- and MMP-9-dependent pathway.
      Conclusions: Collectively, our findings showed that the PRRX1/PPARG2/FFAs signalling in SACC was important for accelerating tumour metastasis through the induction of EMT and the metabolic reprogramming of FFAs.
      (© 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)
    • Comments:
      Erratum in: Cell Prolif. 2021 Oct;54(10):e13118. (PMID: 34590749)
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    • Grant Information:
      81672672 National Natural Science Foundation of China; 81572650 National Natural Science Foundation of China; 81772891 National Natural Science Foundation of China; 81972542 National Natural Science Foundation of China; 2017 Fundamental Research Funds for the Central Universities; 2017JY0024 Sichuan Province Science and Technology Bureau Project; ZR2017BH089 Natural Science Foundation of Shandong Province
    • Contributed Indexing:
      Keywords: PRRX1; free fatty acids (FFAs); metabolism; metastasis; salivary adenoid cystic carcinoma (SACC)
    • Accession Number:
      0 (Fatty Acids)
      0 (Homeodomain Proteins)
      0 (Neoplasm Proteins)
      0 (PRRX1 protein, human)
    • Publication Date:
      Date Created: 20191029 Date Completed: 20200225 Latest Revision: 20210930
    • Publication Date:
      20240104
    • Accession Number:
      PMC6985691
    • Accession Number:
      10.1111/cpr.12705
    • Accession Number:
      31657086