YAP signaling induces PIEZO1 to promote oral squamous cell carcinoma cell proliferation

• DOI: 10.1002/path.5553
• Publication Date: 2020-09-28T11:16:33Z
• Authors: Kana Hasegawa; Shinsuke Fujii; Shinji Matsumoto; Yudai Tajiri; Akira Kikuchi; Tamotsu Kiyoshima
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Squamous Cell Carcinoma of Head and Neck; YAP-Signaling Proteins; Middle Aged; Ion Channels; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Cell Line, Tumor; Humans; Calcium; Female; Mouth Neoplasms; Calcium Signaling; Adaptor Proteins, Signal Transducing; Aged; Cell Proliferation; Transcription Factors

Abstract Most cancer cells are exposed to altered extracellular environments, such as an increase in matrix (ECM) stiffness and soluble signals consisting of growth factors cytokines. It is therefore conceivable that changes tumor environments affect cell behavior. The Hippo pathway reportedly responds the environment regulates nuclear localization transcription co‐activator, yes‐associated protein (YAP)/transcriptional co‐activator with PDZ‐binding motif (TAZ). Inactivation translocation YAP/TAZ stimulates proliferation. Its also gene expression, but precise molecule(s) meditating cell‐proliferating effect YAP signaling on oral squamous carcinoma (OSCC) unclear. First, we examined effects OSCC tumorigenesis. Loss‐of‐function experiments using siRNA or inhibitor, immunohistochemical analyses tissue specimens obtained from patients demonstrated was involved Second, identified Piezo‐type mechanosensitive ion channel component 1 (PIEZO1), a Ca 2+ channel, transcriptional target showed elevated PIEZO1 required for agonist‐dependent entry proliferation cells. Experiments three‐dimensional suspension culture revealed cellular growth. Finally, overexpression nucleus and/or cytoplasm immunohistochemically detected lesions frequent expression both Ki‐67, not non‐tumor regions specimens. These results suggest YAP/PIEZO1 axis promotes © 2020 Pathological Society Great Britain Ireland. Published by John Wiley & Sons, Ltd.