The Tweety homolog (TTYH) chloride channel family is involved in oncogenic processes including cell proliferation, invasion, and colonization of cancers. Among the TTYH family, TTYH1 is highly expressed in several cancer cells, such as glioma, breast, and gastric cancer cells. However, the role of TTYH1 in the progression of osteosarcoma remains unknown. Here, we report that deficient TTYH1 expression results in the inhibition of the migration and invasion of U2OS human osteosarcoma cells. We found that TTYH1 was endogenously expressed at both mRNA and protein levels in U2OS cells and that these channels were located at the plasma membrane of the cells. Moreover, we found that silencing of the TTYH1 with small interfering RNA (siRNA) resulted in a decrease in the migration and invasion of U2OS cells, while the proliferation of the cells was not affected. Additionally, treatment with TTYH1 siRNA significantly suppressed the mRNA expression of epithelial–mesenchymal transition (EMT)-regulated transcription factors such as Zinc E-Box Binding Homeobox 1 (ZEB1) and SNAIL. Most importantly, the expression of matrix metalloproteinase (MMP)-2, MPP-9, and N-cadherin was dramatically reduced following the silencing of TTYH1. Taken together, our findings suggest that silencing of TTYH1 expression reduces migration and invasion of U2OS cells and that TTYH1 may act as a potential molecular target for osteosarcoma treatment.
Bibliographical noteFunding Information:
Funding: This work was supported by the Bio-Synergy Research Project (NRF-2017M3A9C4092979 to J.-Y.P, NRF-2020R1I1A1A01075115 to Y.-S.L.) through the National Research Foundation (NRF) of Korea and partially supported by a Korea University Grant (to Y.-S.L.).
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
- epithelial–mesenchymal transition
ASJC Scopus subject areas
- Ecology, Evolution, Behavior and Systematics
- General Biochemistry,Genetics and Molecular Biology
- Space and Planetary Science