Periostin induces epithelial‑to‑mesenchymal transition via the integrin α5β1/TWIST‑2 axis in cholangiocarcinoma

© 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 ep...

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Main Authors: Jumaporn Sonongbua, Suchada Siritungyong, Suyanee Thongchot, Thanpawee Kamolhan, Kusumawadee Utispan, Peti Thuwajit, Ananya Pongpaibul, Sopit Wongkham, Chanitra Thuwajit
Other Authors: Khon Kaen University
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Published: 2020
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/53611
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spelling th-mahidol.536112020-03-26T12:07:32Z Periostin induces epithelial‑to‑mesenchymal transition via the integrin α5β1/TWIST‑2 axis in cholangiocarcinoma Jumaporn Sonongbua Suchada Siritungyong Suyanee Thongchot Thanpawee Kamolhan Kusumawadee Utispan Peti Thuwajit Ananya Pongpaibul Sopit Wongkham Chanitra Thuwajit Khon Kaen University Mahidol University Thammasat University Faculty of Medicine, Siriraj Hospital, Mahidol University Biochemistry, Genetics and Molecular Biology Medicine © 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. 2020-03-26T04:34:37Z 2020-03-26T04:34:37Z 2020-01-01 Article Oncology Reports. Vol.43, No.4 (2020), 1147-1158 10.3892/or.2020.7485 17912431 1021335X 2-s2.0-85080077626 https://repository.li.mahidol.ac.th/handle/123456789/53611 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85080077626&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Biochemistry, Genetics and Molecular Biology
Medicine
spellingShingle Biochemistry, Genetics and Molecular Biology
Medicine
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
description © 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.
author2 Khon Kaen University
author_facet Khon Kaen University
Jumaporn Sonongbua
Suchada Siritungyong
Suyanee Thongchot
Thanpawee Kamolhan
Kusumawadee Utispan
Peti Thuwajit
Ananya Pongpaibul
Sopit Wongkham
Chanitra Thuwajit
format Article
author Jumaporn Sonongbua
Suchada Siritungyong
Suyanee Thongchot
Thanpawee Kamolhan
Kusumawadee Utispan
Peti Thuwajit
Ananya Pongpaibul
Sopit Wongkham
Chanitra Thuwajit
author_sort Jumaporn Sonongbua
title Periostin induces epithelial‑to‑mesenchymal transition via the integrin α5β1/TWIST‑2 axis in cholangiocarcinoma
title_short Periostin induces epithelial‑to‑mesenchymal transition via the integrin α5β1/TWIST‑2 axis in cholangiocarcinoma
title_full Periostin induces epithelial‑to‑mesenchymal transition via the integrin α5β1/TWIST‑2 axis in cholangiocarcinoma
title_fullStr Periostin induces epithelial‑to‑mesenchymal transition via the integrin α5β1/TWIST‑2 axis in cholangiocarcinoma
title_full_unstemmed Periostin induces epithelial‑to‑mesenchymal transition via the integrin α5β1/TWIST‑2 axis in cholangiocarcinoma
title_sort periostin induces epithelial‑to‑mesenchymal transition via the integrin α5β1/twist‑2 axis in cholangiocarcinoma
publishDate 2020
url https://repository.li.mahidol.ac.th/handle/123456789/53611
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