Publication: Periostin induces epithelial‑to‑mesenchymal transition via the integrin α5β1/TWIST‑2 axis in cholangiocarcinoma
2
Issued Date
2020-01-01
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ISSN
17912431
1021335X
1021335X
Other identifier(s)
2-s2.0-85080077626
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Mahidol University
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SCOPUS
Bibliographic Citation
Oncology Reports. Vol.43, No.4 (2020), 1147-1158
Suggested Citation
Jumaporn Sonongbua, Suchada Siritungyong, Suyanee Thongchot, Thanpawee Kamolhan, Kusumawadee Utispan, Peti Thuwajit, Ananya Pongpaibul, Sopit Wongkham, Chanitra Thuwajit Periostin induces epithelial‑to‑mesenchymal transition via the integrin α5β1/TWIST‑2 axis in cholangiocarcinoma. Oncology Reports. Vol.43, No.4 (2020), 1147-1158. doi:10.3892/or.2020.7485 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/53611
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Title
Periostin induces epithelial‑to‑mesenchymal transition via the integrin α5β1/TWIST‑2 axis in cholangiocarcinoma
Abstract
© 2020 Spandidos Publications. All rights reserved. Periostin (PN) (also known as osteoblast‑specific factor OSF-2) is a protein that in humans is encoded by the POSTN gene and has been correlated with a reduced survival of cholangiocarcinoma (CCA) patients, with the well-known effect of inducing epithelial-to-mesenchymal transition (EMT). The present study investigated the effect of PN, through integrin (ITG)α5β1, in EMT-mediated CCA aggressiveness. The alterations in EMT-related gene and protein expression were investigated by real-time PCR, western blot analysis and zymogram. The effects of PN on migration and the level of TWIST-2 were assessed in CCA cells with and without siITGα5 transfection. PN was found to induce CCA cell migration and EMT features, including increments in Twist‑related protein 2 (TWIST‑2), zinc finger protein SNAI1 (SNAIL-1), α-smooth muscle actin (ASMA), vimentin (VIM) and matrix metallopeptidase 9 (MMP-9), and a reduction in cytokeratin 19 (CK-19) together with cytoplasmic translocation of E-cadherin (CDH-1). Additionally, PN markedly induced MMP-9 activity. TWIST‑2 was significantly induced in PN-treated CCA cells; this effect was attenuated in the ITGα5β1-knockdown cells and corresponded to reduced migration of the cancer cells. These results indicated that PN induced CCA migration through ITGα5β1/TWIST-2-mediated EMT. Moreover, clinical samples from CCA patients showed that higher levels of TWIST‑2 were significantly correlated with shorter survival time. In conclusion, the ITGα5β1-mediated TWIST-2 signaling pathway regulates PN-induced EMT in CCA progression, and TWIST-2 is a prognostic marker of poor survival in CCA patients.