Piezo1 Is as a Novel Trefoil Factor Family 1 Binding Protein that Promotes Gastric Cancer Cell Mobility In Vitro
Abstract
Background Trefoil factor family 1 (TFF1) is a member of the TFF-domain peptide family involved in epithelial restitution and cell motility. Recently, we screened Piezo1 as a candidate TFF1-binding protein. Aim We aimed to confirm Piezo1 as a novel TFF1 binding protein and to assess the role of this interaction in mediating gastric cancer cell mobility. Methods This interaction was confirmed by co-immunoprecipitation and co-localisation of TFF1 and Piezo1 in GES-1 cells. We used stable RNA interference to knockdown Piezo1 protein expression and restored the expression of TFF1 in the gastric cancer cell lines SGC-7901 and BGC-823. Cell motility was evaluated using invasion assay and migration assay in vitro. The expression levels of the integrin subunits β1, β5, α1 as well as the expression of β-catenin and E-cadherin were detected by Western blot. Results We demonstrate that TFF1, but not TFF2 or TFF3, bind to and co-localize with Piezo1 in the cytoplasm in vitro. TFF1 interacts with the C-terminal portion of the Piezo1 protein. Wound healing and trans-well assays demonstrated that the restored expression of TFF1 promoted cell mobility in gastric cancer cells, and this effect was attenuated by the knockdown of Piezo1. Western blots demonstrated the decreased expression of integrin β1 in Piezo1-knockdown cells. Conclusions Our data demonstrate that Piezo1 is a novel TFF1 binding protein that is important for TFF1-mediated cell migration and suggest that this interaction may be a therapeutic target in the invasion and metastasis of gastric cancer.
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In vitro, Piezo1 reduces the migratory ability of gastric cancer cells by downregulating integrin β subunits.
“In vitro, Piezo1 has been shown to reduce the migratory ability of gastric cancer cells by downregulating integrin β subunits.108”
From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [108]
In other cancers, such as NSCLC and gastric cancer, Piezo1 expression is often reduced and has been shown to inhibit cell migration and metastasis, potentially via integrin-mediated and Hippo-pathway-related mechanisms.
“Conversely, in other cancers, such as non-small cell lung carcinoma and gastric cancer, Piezo1 expression is often reduced and has been shown to inhibit cell migration and metastasis, potentially via integrin-mediated and Hippo-pathway-related mechanisms.”
From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [108]
Gastric cancer exhibits a distinct integrin-Piezo1-FAK axis, with rigidity-induced FAK phosphorylation enhancing migration.
“Gastric cancer exhibits a distinct integrin-Piezo1-FAK axis, with rigidity-induced FAK phosphorylation enhancing migration.”
From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [108]
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Blythe, N. M. (2019) · White Rose eTheses Online (University of Leeds, The University of Sheffield, University of York)
- Authors
- Yang, X.-N., Lu, Y.-P., Liu, J.-J., Huang, J.-K., Liu, Y.-P., Xiao, C.-X., Jazag, A., Ren, J.-L., & Guleng, B.
- Affiliations
- Xiamen University (CN)
- National Institute for Medical Research (TZ)
- Corresponding author
- Guleng, Bayasi
- Venue
- Digestive Diseases and Sciences
- Published
- 2014-05-06
- Volume
- 59
- Issue
- 7
- Pages
- 1428-1435
- ISSN
- 0163-2116 (ISSN-L)
- 1573-2568
- OpenAlex
- W2012045650
- Cited by
- 112
- References
- 28
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 12 · 2023: 12 · 2022: 20 · 2021: 15 · 2020: 8 · 2019: 12 · 2018: 7 · 2017: 4 · 2016: 1 · 2015: 5 · 2014: 2
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Digestive Diseases and Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Piezo1, TFF1, gastric cancer, cell migration, cell invasion, protein-protein interaction, beta1 integrin, epithelial restitution, metastasis, therapeutic target
- MeSH terms
- Trefoil Factor-1, Trefoil Factor-2, Carrier Proteins, Cell Movement, Humans, Ion Channels, Stomach Neoplasms, Biomarkers, Tumor, Blotting, Western, Tumor Suppressor Proteins, Cell Line, Tumor, Immunoprecipitation, Gene Knockdown Techniques
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