Hippo pathway induces PIEZO1 expression to promote oral squamous cell carcinoma cell proliferation
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ABSTRACT:
PROVIDER: PRJNA630987 | ENA |
REPOSITORIES: ENA
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Project description:Most cancer cells are exposed to extracellular environments, such as extracellular matrix, which commonly becomes stiffer along with transformation. It is conceivable that tumorous extracellular environments would be changing to affect tumor cell behavior. It has been reported that Hippo pathway responds to the extracellular environments and induces the nuclear localization of transcription activator, yes-associated protein (YAP), resulting in stimulating cell proliferation. Its pathway also regulates gene expression, but the precise molecule to meditate cell proliferating effect of Hippo pathway in oral squamous cell carcinoma (OSCC) is not well understood. Here, we examined the effects of YAP-mediated Hippo pathway in OSCC tumorigenesis. Loss-of-function experiments using siRNA or an inhibitor, and immunohistochemical analyses of tissue specimens obtained from OSCC specimens demonstrated that YAP-mediated Hippo pathway was involved in OSCC cell proliferation. We identified Piezo-type mechanosensitive ion channel component 1 (PIEZO1), a Ca2+ channel, as a downstream molecule of Hippo pathway and showed that elevated PIEZO1 expression was required for PIEZO1 agonist-dependent Ca2+ entry and cell proliferation in OSCC cells. Furthermore, the experiments using three-dimensional culture and suspension culture revealed that PIEZO1, of which expression was regulated by YAP-mediated Hippo pathway, was involved in OSCC cellular growth. Immunohistochemically, YAP overexpression with nucleus and/or cytoplasm was detected with both PIEZO1 and Ki-67 expression at high frequencies in tumor lesion, but not in non-tumor region, of OSCC specimens. These results suggest that the YAP-mediated Hippo/PIEZO1 axis, which might be activated by the tumorous extracellular environments, promotes OSCC tumor cell growth.
2020-05-08 | GSE150044 | GEO
Project description:An investigation of canine oral squamous cell carcinomas
2024-06-30 | PRJEB77007 | EVA
Project description:PIEZO1 is a mechanically-activated ion channel that contributes to flow sensing in vascular endothelium. Moreover, deletion of endothelial PIEZO1 was recently found to suppress activation of Notch1 target genes in hepatic microvascular endothelium. Here, because of the liver’s dominant role in lipid regulation, we set out to test the novel hypothesis that endothelial PIEZO1 regulates hepatic lipid homeostasis. We performed bulk RNA sequencing on PIEZO1-deleted mice exposed to chow and high fat diets. Our transcriptomics analysis reveal unexpected relevance to lipid and glucose homeostasis.
2024-06-29 | E-MTAB-9996 | biostudies-arrayexpress
Project description:Extracellular biophysical cues such as matrix stiffness are key stimuli tuning cell fate and affecting tumor progression in vivo. However, it remains unclear how spheroids in a 3D microenvironment perceive matrix mechanical stiffness stimuli and translate them into intracellular signals driving cancer. Mechanosensitive Piezo1 and TRPV4 ion channels, upregulated in many malignancies, are major transducers of such physical stimuli into biochemical responses. Most mechanotransduction studies probing the reception of changing stiffness cues by cells are, however, still limited to 2D culture systems or cell-extracellular matrix models which lack the major cell-cell interactions prevalent in 3D cancer tumors. Here, we engineered a 3D spheroid culture environment with varying mechanobiological properties to study the effect of static matrix stiffness stimuli on mechanosensitive and malignant phenotypes in oral squamous cell carcinoma spheroids. We find that spheroid growth is enhanced when cultured in stiff extracellular matrix. Using flow cytometry, we show that the expression of mechanoreceptor Piezo1 and stemness marker CD44 is upregulated in stiff matrix. We also report the upregulation of a selection of genes with associations to mechanoreception, ion channel transport, extracellular matrix organization, and tumorigenic phenotypes in stiff matrix spheroids. Together, our results indicate that cancer cells in 3D spheroids utilize mechanosensitive ion channels Piezo1 and TRPV4 to sense changes in static extracellular matrix stiffness and that stiffness drives pro-tumorigenic phenotypes in oral squamous cell carcinoma.
2024-03-28 | GSE262142 | GEO
Project description:In gastric cancer (GC), PIEZO1 was suggested to promote cell migration by interacting with Trefoil factor family 1 (TFF1) and serve as a therapeutic target against invasion and metastasis. In addition, PIEZO1 demonstrates abundant expression in most GC cell lines and primary samples and highly-expressed PIEZO1 is associated with poor disease-specific survival. As Yoda1 is known to be an agonist of PIEZO1, we try to explore the PIEZO1 function in GC by Yoda1 treatment.
2023-12-08 | GSE228691 | GEO
Project description:The propeller-shaped blades of the PIEZO1 and PIEZO2 ion channels partition into the plasma membrane and respond to indentation or stretching of the lipid bilayer, thus converting mechanical forces into signals that can be interpreted by cells, in the form of calcium flux and changes in membrane potential. While PIEZO channels participate in diverse physiological processes, from sensing the shear stress of blood flow in the vasculature to detecting a light touch on the surface of the skin, the molecular details that enable these mechanosensors to tune their responses over a vast dynamic range of forces remain largely uncharacterized. To survey the molecular landscape surrounding PIEZO channels at the cell surface, we employed a mass spectrometry-based proteomic approach to capture and identify extracellularly exposed proteins in the vicinity of PIEZO1. This PIEZO1-proximal interactome was enriched in surface proteins localized to cell junctions and signaling hubs within the plasma membrane. Functional screening of these interaction candidates by calcium imaging and electrophysiology in an overexpression system identified the adhesion molecule CADM1/SynCAM that slows the inactivation kinetics of PIEZO1 with little effect on PIEZO2. Conversely, we found that CADM1 knockdown accelerates inactivation of endogenous PIEZO1 in Neuro-2a cells. Systematic deletion of CADM1 domains indicate that the transmembrane region is critical for the observed effects on PIEZO1, suggesting that modulation of inactivation is mediated by interactions in or near the lipid bilayer.
2024-10-30 | PXD054618 | Pride
Project description:Oral tongue squamous cell carcinoma (OTSCC) is a highly malignant type of tumor. The 5-year survival rate of patients with advanced tongue squamous cell carcinoma is only ~50%. Pyruvate kinase M2 (PKM2) is the key rate-limiting enzyme of glycolysis, maintaining the Warburg effect in tumor cells. The present study aimed to investigate the relationship between PKM2 expression and the poor prognosis of patients with OTSCC and to determine oral squamous carcinoma tumor cell proliferation and apoptosis. Reverse transcription-quantitative (RT-q) PCR, western blotting and immunohistochemistry were used to analyze the expression levels of PKM2 in OTSCC, and the clinicopathological characteristics and prognosis of patients with OTSCC were further analyzed by statistical analysis. The results from RT-qPCR and immunohistochemistry demonstrated that PKM2 was upregulated in OTSCC tissues and highly expressed in advanced stage OTSCC tissues compared with paired adjacent tissues and lower stage OTSCC tissues. Patients with OTSCC and high PKM2 expression had shorter overall survival (OS) compared with those with low PKM2 expression. Furthermore, high expression of PKM2 was significantly associated with Tumor-Node-Metastasis (TNM) stage. TNM stage and PKM2 expression were independent predictive factors for OS in patients with OTSCC. In addition, PKM2 knockdown inhibited the proliferation and increased the apoptosis of oral squamous carcinoma tumor cells. Furthermore, PKM2 knockdown could regulate the expression of cell cycle and apoptosis-related proteins by activating Hippo signaling pathway, as confirmed by the decreased expression of yes-associated protein 1 (YAP), Bcl-2 and Ki-67 and the increased expression of large tumor suppressor kinase 1, phosphorylated YAP and Bax. Taken together, the findings from this study demonstrated that PKM2 may be considered as a potential target for the diagnosis and treatment of OTSCC.
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Project description:Macrophages play a pivotal role in mechanical force-induced inflammatory bone remodeling. Yet, how macrophages perceive mechanical stimuli and thereby modulate biological behaviors remain elusive. The orthodontic tooth movement (OTM) model was established to access the role of Piezo1 in modulating macrophage response upon mechanical stimuli. The potential functions and molecule mechanisms of Piezo1 were explored by bone marrow-derived macrophages (BMDMs) using mechanical stretch system, western blotting, immunofluorescence, flow cytometry and RNA sequencing. We first found macrophage proliferative phenotype enhanced at the later stage of force application. The biological variation mediated by mechanical force could be suppressed by Piezo1 inhibition. Furthermore, Piezo1 activated PI3K-AKT signaling was closely associated with macrophage proliferation upon mechanical stimuli. Additionally, Ccnd1 was authenticated as a critical downstream factor of PI3K-AKT signaling and conditional ablation of Ccnd1 in macrophages inhibited macrophage proliferation in mechanical force-induced bone remodeling procedure.
2024-12-08 | GSE190470 | GEO
Project description:In gastric cancer (GC), PIEZO1 was suggested to promote cell migration by interacting with Trefoil factor family 1 (TFF1) and serve as a therapeutic target against invasion and metastasis. In addition, PIEZO1 demonstrates abundant expression in most GC cell lines and primary samples and highly-expressed PIEZO1 is associated with poor disease-specific survival. Thus, we try to explore the PIEZO1 function in GC by knocking down assay.
2023-12-08 | GSE228690 | GEO
Project description:Identification of CMTM6 as a novel mediator of cisplatin resistance in oral squamous cell carcinoma
2020-01-07 | MSV000084761 | MassIVE