The function of Piezo1 in colon cancer metastasis and its potential regulatory mechanism

Abstract

Objective Increasing evidence has revealed that mechanical stress and elevated mechanical signals promote malignant tumor transformation and metastasis. This study aimed to explore the function of the mechanically activated ion-channel Piezo1 in the colon cancer metastasis and its potential regulatory mechanism. Methods First, we examined the expression levels of Piezo1 and mitochondrial calcium uniporter (MCU) both in colon cancer tissues and assessed the prognostic value of Piezo1 and MCU in a colon cancer cohort (n = 110). Second, functional assays were performed to investigate the effects of Piezo1 and MCU on colon cancer cell migration, invasion, and mitochondrial membrane potential. Third, we analyzed the expression of Piezo1, MCU, and HIF-1α by overexpressing/silencing each other's expression. Results We found that Piezo1 was up-regulated and MCU was down-regulated in colon cancer tissues. Piezo1 and MCU were both correlated with poor prognosis of patients with colon cancer. Overexpressing Piezo1 and silencing MCU could promote colon cancer cell migration and metastasis, reduce mitochondrial membrane potential, and promote each other's expression. We also found that HIF-1α was up-regulated in colon cancer tissues. Additionally, silencing Piezo1 inhibited the expression of HIF-1α and VEGF, which was contrary to MCU silencing. Intriguingly, Piezo1-overexpressing cells did not regain their migration behaviors when HIF-1α expression was inhibited, which was accompanied with the re-expression of MCU and VEGF. Conclusion In our study, Piezo1 is involved in colon cancer cell metastasis. Furthermore, our findings indicated a possible Piezo1-MCU-HIF-1α-VEGF axis, which still need further exploration.Keywords Colon cancer · Metastasis · Piezo1 · Mitochondrial calcium uniporter · HIF-1α Yanhua Sun and Ming Li have contributed equally to this work.

<p>The Regulatory Mechanism and Biological Significance of Mitochondrial Calcium Uniporter in the Migration, Invasion, Angiogenesis and Growth of Gastric Cancer</p>

“…Intriguingly, our results indicated that MCU expression was significantly higher in omental metastasis than gastric cancer tissues, indicating that MCU expression might contribute to gastric cancer metastasis. Combining previous studies, MCU has been confirmed to promote several cancer metastasis, such as colon cancer 10 and hepatocellular carcinoma. 11 We found that MCU knockdown In gastric cancer tissues, there was an increase in expression of HIF-1α and Vimentin and loss of E-cadherin.…”

“…As previous studies, MCU expression is associated with HIF-1α signaling pathway in TNBC 8 and colon cancer. 10 Thus, in this study, we detected the expression of MCU, submit your manuscript | www.dovepress.com…”

“…9 Abnormally expressed MCU is associated with poor prognosis of colon cancer patients. 10 MCU knockdown can promote the migration and metastasis of colon cancer cells and reduce the mitochondrial membrane potential. MCU is dysregulated in hepatocellular carcinoma cells and is closely related to the metastasis and poor prognosis of patients with hepatocellular carcinoma.…”

Structure, kinetic properties and biological function of mechanosensitive Piezo channels

“…As tumor cells grow, the mechanical forces within the tumor and TME increase, and the mechanosensitive cation channels are activated by these mechanical signals and interact with focal adhesions to regulate tumor development [ 171 ]. Recent research showed that the Piezo1 channel is closely correlated with some types of cancers, including oral squamous cell carcinoma, prostate cancer and colon cancer [ 172 – 174 ]. Furthermore, the Piezo2 channel has been shown to play a role in the proliferative changes and angiogenesis of brain metastatic cells and bladder cancer [ 175 ].…”

pH-Channeling in Cancer: How pH-Dependence of Cation Channels Shapes Cancer Pathophysiology

“…The Piezo1 channel enhances the invasive phenotype in multiple tumors, namely breast, colorectal and prostate cancers [ 193 , 287 , 288 ]. An electrophysiological study described that heterologously expressed Piezo1 channels are inhibited by extracellular protons [ 188 ].…”