Piezo1 impairs hepatocellular tumor growth via deregulation of the MAPK-mediated YAP signaling pathway

Liu, Silin; Xu, Xiao‐Huang; Fang, Zhigang; Ning, Yile; Deng, Bo; Pan, Xiaobo; He, Yu; Yang, Zhong-Qi; Huang, Keer; Li, Jing

doi:10.1016/j.ceca.2021.102367

Cited by 54 publications

(35 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EMT is one of the key mechanisms of TGF-β signaling regulating cancer progression [47][48][49]. Lately, one research has proved that downregulated Piezo1 could impairs HCC growth via deregulation of the MAPK-mediated YAP signaling pathway in HepG2 cell line and in Vivo [50]. Unlikely, our research revealed the prognostic value of Piezo1 and more concern about invasion and migration of HCC, and GSEA in our research indicates that EMT and TGF-β signaling regulated by Piezo1, but not MAPK or YAP signaling, and we also veri ed it in clinical specimens.…”

Section: Discussionmentioning

confidence: 99%

Piezo1 Promoted Hepatocellular Carcinoma Progression and EMT Through Activating TGF-β Signaling by Recruiting Rab5c

Sun

et al. 2021

Preprint

View full text Add to dashboard Cite

Background Piezo1 plays critical roles in vascular development during early embryogenesis. However, the function of Piezo1 in hepatocellular carcinoma (HCC) remain elusive. This study aimed to explore the function and mechanisms of Piezo1 in HCC. Methods qRT-PCR, western blot and immunohistochemistry analyses were used to determine Piezo1 expression in HCC samples and cell lines. The clinical significance of Piezo1 was assessed in two independent study cohorts containing 280 patients with HCC. Gene set enrichment analysis (GSEA) was performed to explore the signaling pathway of Piezo1. A series of in vitro and in vivo experiments were used to determine the role and molecular mechanism of Piezo1 in HCC progression. Results Piezo1 expression was significantly upregulated in HCC tissues and cell lines. High Piezo1 expression was closely correlated with aggressive clinicopathological features, poor clinical outcomes of HCC patients. Moreover, knockdown of Piezo1 in HCCLM3 and Hep3B cells significantly inhibited proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of HCC cells in vitro, and tumor growth, EMT and metastasis in vivo. Further mechanism study indicated that these phenotypic and function changes were mediated by TGF-β signaling pathway. Finally, we proved that Piezo1 exerted its tumor promotion effect by recruiting Rab5c to activating TGF-β signaling pathway. Conclusions We proved Piezo1 promotes progression of hepatocellular carcinoma via TGF-β signaling, which may serve as a novel prognostic predictor and the potential therapeutic target for HCC patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Piezo1 Promoted Hepatocellular Carcinoma Progression and EMT Through Activating TGF-β Signaling by Recruiting Rab5c

Sun

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Calpain2, a calciumdependent protease, is a member of the calpain families which can be activated by increased intracellular calcium. Inhibition of Piezo1 by Piezo-siRNA or GsMTx4 could reduce calpain activity in HepG2 cells or PC12 cells (36,37). Calcium-calpain2 pathway was thus examined in our study.…”

Section: Activation Of Piezo1 Induced Calcium Influx and Enhanced Int...mentioning

confidence: 95%

“…As shown in Figure 9, Yoda1 increased protein abundance of calpain2 in HK2 cells (Figure 9C-F). Piezo1 inhibition by siRNA attenuated Yoda1-induced upregulation of calpain2 (Figure 9E and F), indicating that calpain2 was an important downstream of Piezo1 (36)(37)(38). Piezo1 mediated calcium response seems largely dependent on extracellular calcium levels.…”

Section: Activation Of Piezo1 Induced Calcium Influx and Enhanced Int...mentioning

confidence: 97%

Mechanosensitive Piezo1 channels mediate renal fibrosis

Zhao¹,

Kong²,

Liang³

et al. 2022

JCI Insight

Self Cite

View full text Add to dashboard Cite

Kidney fibrosis is the final common pathway of progressive kidney diseases, the underlying mechanisms of which is not fully understood. The purpose of the current study is to investigate a role of Piezo1, a mechanosensitive nonselective cation channel, in kidney fibrosis. In human fibrotic kidneys, Piezo1 protein expression was markedly upregulated. The abundance of Piezo1 protein in kidneys of mice with UUO or with folic-acid treatment was significantly increased. Inhibition of Piezo1 with GsMTx4 markedly ameliorated UUO or folic acid-induced kidney fibrosis. Mechanical stretch, compression or stiffness induced Piezo1 activation and pro-fibrotic responses in human HK2 cells and primary cultured mouse proximal tubular cells (mPTCs), which were greatly prevented by inhibition or silence of Piezo1. TGFβ-1 induced increased Piezo1 expression and pro-fibrotic phenotypic alterations in HK2 cells and mPTCs, which was again markedly prevented by inhibition of Piezo1. Activation of Piezo1 by Yoda1, a Piezo1 agonist, caused calcium influx and profibrotic responses in HK2 cells and induced calpain2 activation, followed by talin1 cleavage and upregulation of integrinβ1. Also, Yoda1 promoted the link between ECM and integrinβ1. In conclusion, Piezo1 is involved in the progression of kidney fibrosis and pro-fibrotic alterations in renal proximal tubular cells, likely through activating calcium-calpain2-integrinβ1 pathway.

show abstract

“…The function of Piezo1 and its downstream mechanism have obvious differences in various tissue inflammations. Piezo1-mediated Ca 2+ signaling participates in the occurrence and development of inflammation through a variety of signaling pathways ( Table 1 ), including the classic inflammation pathway Jak/Stat: IL-6 receptor family ( 56 , 120 ), TLR ( 9 , 42 ) and NF-κB ( 66 , 117 , 121 ); Inflammasome NLRP3 ( 66 , 95 ); Ca 2+ -sensitive MAPK family (ERK, JNK, P38) ( 116 , 120 , 122 , 123 ), AKT/mTOR ( 60 , 69 )、β1 integrin ( 18 ); As well as focal adhesion kinase (FAK) related to inflammation-related mechanical transformation ( 60 , 124 ), proline-rich tyrosine kinase2 (Pyk2) ( 125 ); Calcineurin (RACK1), calcium/calmodulin-dependent protein kinase II (CaMKII-Mst1/2-Rac) and calpain1 ( 18 ). Although the downstream mechanisms involved in Piezo1 are different in different organizations and occasions, they all eventually lead to inflammatory events.…”

Section: Mechanism Of Piezo1 Transducing Inflammatory Signalsmentioning

confidence: 99%

Piezo1 Channels as Force Sensors in Mechanical Force-Related Chronic Inflammation

Liu

Zheng

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Mechanical damage is one of the predisposing factors of inflammation, and it runs through the entire inflammatory pathological process. Repeated or persistent damaging mechanical irritation leads to chronic inflammatory diseases. The mechanism of how mechanical forces induce inflammation is not fully understood. Piezo1 is a newly discovered mechanically sensitive ion channel. The Piezo1 channel opens in response to mechanical stimuli, transducing mechanical signals into an inflammatory cascade in the cell leading to tissue inflammation. A large amount of evidence shows that Piezo1 plays a vital role in the occurrence and progression of chronic inflammatory diseases. This mini-review briefly presents new evidence that Piezo1 responds to different mechanical stresses to trigger inflammation in various tissues. The discovery of Piezo1 provides new insights for the treatment of chronic inflammatory diseases related to mechanical stress. Inhibiting the transduction of damaging mechanical signals into inflammatory signals can inhibit inflammation and improve the outcome of inflammation at an early stage. The pharmacology of Piezo1 has shown bright prospects. The development of tissue-specific Piezo1 drugs for clinical use may be a new target for treating chronic inflammation.

show abstract

Piezo1 impairs hepatocellular tumor growth via deregulation of the MAPK-mediated YAP signaling pathway

Cited by 54 publications

References 51 publications

Piezo1 Promoted Hepatocellular Carcinoma Progression and EMT Through Activating TGF-β Signaling by Recruiting Rab5c

Piezo1 Promoted Hepatocellular Carcinoma Progression and EMT Through Activating TGF-β Signaling by Recruiting Rab5c

Mechanosensitive Piezo1 channels mediate renal fibrosis

Piezo1 Channels as Force Sensors in Mechanical Force-Related Chronic Inflammation

Contact Info

Product

Resources

About