PIEZO1 functions as a potential oncogene by promoting cell proliferation and migration in gastric carcinogenesis

Abstract

Gastric cancer (GC) is one of the most common malignancies in Asian areas. PIEZO1 has been implied to regulate epithelial homeostasis to play an important role in physiological processes. It is also related to tumor initiation and progression. However, the role of PIEZO1 has not yet been explored in GC. The expression of PIEZO1 in GC cell lines and primary samples was determined by qRT-PCR and Western blot. The clinical correlation of PIEZO1 in GC was evaluated by immunohistochemistry on tissue microarray. The oncogenic role of PIEZO1 was demonstrated in gastric tumorigenesis through a series of functional assays, including cell proliferation, cell invasion, and flow cytometry analysis. Drug sensitivity was also assessed by PIEZO1 knockdown experiment. PIEZO1 exhibited an upregulation in most of the GC cell lines and primary samples compared with non-tumorous gastric epithelial tissues. Increase of PIEZO1 was associated with poor disease specific survival. PIEZO1 knockdown led to inhibitory effect by suppressing cell proliferation and invasion and inhibiting xenograft formation. Decreased PIEZO1 enhanced the sensitivity of Cisplatin or 5-FU treatment. Morphological alteration was also observed in siPIEZO1 treated cells. GTP-Rac1 showed accumulated activated form, while total-RhoA was decreased accompanied with PIEZO1 knockdown. In the present study, PIEZO1 is required for cell proliferation, migration and invasion to promote GC progression. PIEZO1 also maintains cellular morphology related to GC cell motility by regulating the activity of Rho GTPase family members. Our data not only suggested a novel prognostic marker, but also provided a useful clinical therapeutic target for GC.

Chemical activation of the Piezo1 channel drives mesenchymal stem cell migration via inducing ATP release and activation of P2 receptor purinergic signaling

“…Recent studies have reported a role for the Piezo1 channel in regulating cell migration in endothelial cell and cancer cells . In this study, we provide evidence to show that the Piezo1 channel plays a similar role in hDP‐MSCs.…”

“…To test whether the Piezo1 channel plays a role in regulating hDP‐MSC migration, as recently reported in endothelial cell and various cancer cells, we used the wound healing assay to examine the effect of Yoda1 on cell migration (Figure ). Inclusion of 0.1‐1 μM Yoda1 in the culture medium resulted in a concentration‐dependent increase in cell migration, with 0.3 and 1 μM Yoda1 significantly accelerating cell migration at 24, 48, and 72 hours, and such stimulation was observed in hDP‐MSCs from all four donors, with some variations among the different donors (Figure A‐F).…”

“…MSCs are mechanosensitive, and mechanical forces can induce ATP release, but the mechanisms for mechanical induction of ATP release from MSCs remain poorly understood . The Ca 2+ ‐permeable Piezo1 channel is a newly discovered mechanosensing mechanism in many types of cells . Furthermore, recent studies have reported that mechanical or chemical activation of the Piezo1 channel induces ATP release from endothelial cells, urothelial cells, and red blood cells .…”

“…Furthermore, recent studies have reported that mechanical or chemical activation of the Piezo1 channel induces ATP release from endothelial cells, urothelial cells, and red blood cells . There is also compelling evidence to support a critical role for the Piezo1 channel in regulating cell migration in endothelial cells, breast cancer cells, gastric cancer cells, and small lung cancer cells . Recent studies have also shown the expression of the Piezo1 channel in human bone marrow‐derived MSCs (BM‐MSCs) and rat dental pulp‐derived stem cells (DP‐MSCs) .…”

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

“…The most important biological feature of malignant tumors, including colon cancer, is the invasion and metastasis of tumor cells. Piezo1 is involved in gastric cancer cell migration and invasion (Yang et al 2014;Zhang et al 2018). Our findings revealed that overexpressed Piezo1 promoted colon cancer cell migration and motility.…”