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<scp>YAP</scp> signaling induces <scp>PIEZO1</scp> to promote oral squamous cell carcinoma cell proliferation
- Source :
- The Journal of Pathology. 253:80-93
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Most cancer cells are exposed to altered extracellular environments, such as an increase in extracellular matrix (ECM) stiffness and soluble signals consisting of growth factors and cytokines. It is therefore conceivable that changes in tumor extracellular environments affect tumor cell behavior. The Hippo pathway reportedly responds to the extracellular environment and regulates the nuclear localization of the transcription co-activator, yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ). Inactivation of the Hippo pathway with nuclear translocation of YAP/TAZ stimulates cell proliferation. Its pathway also regulates gene expression, but the precise molecule(s) meditating the cell-proliferating effect of YAP signaling on oral squamous cell carcinoma (OSCC) is unclear. First, we examined the effects of YAP signaling on OSCC tumorigenesis. Loss-of-function experiments using siRNA or an inhibitor, and immunohistochemical analyses of tissue specimens obtained from OSCC patients demonstrated that YAP signaling was involved in OSCC cell proliferation. Second, we identified Piezo-type mechanosensitive ion channel component 1 (PIEZO1), a Ca2+ channel, as a transcriptional target of YAP signaling and showed that elevated PIEZO1 was required for PIEZO1 agonist-dependent Ca2+ entry and cell proliferation in OSCC cells. Experiments using three-dimensional and suspension culture revealed that PIEZO1 was involved in OSCC cellular growth. Finally, YAP overexpression in the nucleus and/or cytoplasm was immunohistochemically detected in tumor lesions with frequent expression of both PIEZO1 and Ki-67, but not in non-tumor regions of OSCC specimens. These results suggest that the YAP/PIEZO1 axis promotes OSCC cell growth. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- Subjects :
- Adult
Male
0301 basic medicine
medicine.disease_cause
Ion Channels
Pathology and Forensic Medicine
Extracellular matrix
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Extracellular
medicine
Humans
Calcium Signaling
Adaptor Proteins, Signal Transducing
Aged
Cell Proliferation
Aged, 80 and over
Hippo signaling pathway
Squamous Cell Carcinoma of Head and Neck
Cell growth
Chemistry
PIEZO1
YAP-Signaling Proteins
Middle Aged
Gene Expression Regulation, Neoplastic
stomatognathic diseases
030104 developmental biology
Cytoplasm
030220 oncology & carcinogenesis
Cancer cell
Cancer research
Calcium
Female
Mouth Neoplasms
Carcinogenesis
Transcription Factors
Subjects
Details
- ISSN :
- 10969896 and 00223417
- Volume :
- 253
- Database :
- OpenAIRE
- Journal :
- The Journal of Pathology
- Accession number :
- edsair.doi.dedup.....04a9ee84a5ee45cf0e521e6c9efa3706