The role of Piezo1 mechanotransduction in high-grade serous ovarian cancer: Insights from an in vitro model of collective detachment.

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  • Additional Information
    • Source:
      Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]-
    • Subject Terms:
      Ion Channels*/metabolism ; Ion Channels*/genetics ; Mechanotransduction, Cellular* ; Ovarian Neoplasms*/metabolism ; Ovarian Neoplasms*/pathology ; Ovarian Neoplasms*/genetics ; Spheroids, Cellular*/metabolism; Animals ; Female ; Humans ; Mice ; Cell Line, Tumor ; Cystadenocarcinoma, Serous/metabolism ; Cystadenocarcinoma, Serous/pathology ; Cystadenocarcinoma, Serous/genetics ; Neoplasm Grading
    • Abstract:
      Slowing peritoneal spread in high-grade serous ovarian cancer (HGSOC) would improve patient prognosis and quality of life. HGSOC spreads when single cells and spheroids detach, float through the peritoneal fluid and take over new sites, with spheroids thought to be more aggressive than single cells. Using our in vitro model of spheroid collective detachment, we determine that increased substrate stiffness led to the detachment of more spheroids. We identified a mechanism where Piezo1 activity increased MMP-1/MMP-10, decreased collagen I and fibronectin, and increased spheroid detachment. Piezo1 expression was confirmed in omental masses from patients with stage III/IV HGSOC. Using OV90 and CRISPR-modified PIEZO1 -/- OV90 in a mouse xenograft model, we determined that while both genotypes efficiently took over the omentum, loss of Piezo1 significantly decreased ascitic volume, tumor spheroids in the ascites, and the number of macroscopic tumors in the mesentery. These results support that slowing collective detachment may benefit patients and identify Piezo1 as a potential therapeutic target.
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    • Grant Information:
      P30 CA014520 United States CA NCI NIH HHS; R01 CA232517 United States CA NCI NIH HHS; R01 CA240965 United States CA NCI NIH HHS
    • Accession Number:
      0 (Ion Channels)
      0 (PIEZO1 protein, human)
      0 (Piezo1 protein, mouse)
    • Publication Date:
      Date Created: 20240426 Date Completed: 20240426 Latest Revision: 20240912
    • Publication Date:
      20240912
    • Accession Number:
      PMC11051664
    • Accession Number:
      10.1126/sciadv.adl4463
    • Accession Number:
      38669327