Piezo1 Is as a Novel Trefoil Factor Family 1 Binding Protein that Promotes Gastric Cancer Cell Mobility In Vitro
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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.
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.
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.
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.
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.
KeywordsTFF1 TFF1 binding protein Piezo1 Cell migration
Trefoil factor family-1
Thromboxane A2 receptor
Short interfering RNA
This study was supported by National Natural Science Foundation of China (No. 81370505, 81370591 & 91229201), Key Projects for Technology Plan of Xiamen (No. 3502Z20100002) and Ministry of Health Foundation for State Key Clinical Department in China.
Conflict of interest
- 3.May FEB, Griffin SM, Westley BR. The trefoil factor interacting protein TFIZ1 binds the trefoil protein TFF1 preferentially in normal gastric mucosal cells but the co-expression of these proteins is deregulated in gastric cancer. Int J Biochem Cell Biol. 2009;41:632–640.PubMedCentralPubMedCrossRefGoogle Scholar
- 21.Fukuda K, Saikawa Y, Yagi H, Wada N, Takahashi T, Kitagawa Y. Role of integrin alpha1 subunits in gastric cancer patients with peritoneal dissemination. Mol Med Report. 2012;5:336–340.Google Scholar