{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:06:15Z","timestamp":1792166775224,"version":"4.4.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The Hippo pathway consists of mammalian sterile 20-like kinase 1\/2 (MST1\/2), large tumor suppressor 1\/2 (LATS1\/2), and yes-associated protein (YAP)1. Herein, we present the first report on the significance of major Hippo pathway protein expression in oral squamous cell carcinoma (OSCC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The analyses included oral epithelial dysplasia (OED, <jats:italic>n<\/jats:italic>\u2009=\u20097), carcinoma <jats:italic>in situ<\/jats:italic> (CIS, <jats:italic>n<\/jats:italic>\u2009=\u200914), and oral squamous cell carcinoma (OSCC, <jats:italic>n<\/jats:italic>\u2009=\u2009109).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cytoplasmic expression of MST1, LATS1, and LATS2 was low in OED, CIS, and OSCC. The cytoplasmic expression of MST2 was high in OED (5\/7 cases), CIS (9\/14 cases), and poorly differentiated OSCC (8\/8 cases) but was low\/lost in a proportion of differentiated OSCC (60\/101 cases). The expression of YAP1 was associated with differentiation; low YAP expression was significantly more frequent in well-differentiated OSCC (35\/71 cases), compared to moderately and poorly differentiated OSCC (11\/38 cases). An infiltrative invasion pattern was associated with a high expression of MST2 and high expression of YAP1. The high expression of YAP1 was associated with features of epithelial-to-mesenchymal transition (EMT), such as the loss of E-cadherin and high expression of vimentin, laminin 5, and Slug. High expression of protein arginine methyltransferase (PRMT) 1 or 5, which positively regulates YAP activity, was associated with the high expression of YAP1 (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Among the major Hippo pathway proteins, MST2 displayed a distinctive expression pattern in a significant proportion of differentiated OSCC, suggesting a possible differential role for MST2 depending on the course of OSCC progression. A high YAP1 expression may indicate aggressive OSCC with EMT via PRMTs at the invasive front.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2024.1247625","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T05:21:52Z","timestamp":1708406512000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["The significance of Hippo pathway protein expression in oral squamous cell 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