Periostin activates integrin α5β1 through a PI3K/AKT‑dependent pathway in invasion of cholangiocarcinoma

Utispan,Kusumawadee; Sonongbua,Jumaporn; Thuwajit,Peti; Chau-In,Siri; Pairojkul,Chawalit; Wongkham,Sopit; Thuwajit,Chanitra

doi:10.3892/ijo.2012.1530

Periostin activates integrin α5β1 through a PI3K/AKT‑dependent pathway in invasion of cholangiocarcinoma

Authors:
- Kusumawadee Utispan
- Jumaporn Sonongbua
- Peti Thuwajit
- Siri Chau-In
- Chawalit Pairojkul
- Sopit Wongkham
- Chanitra Thuwajit
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Affiliations: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
Published online on: June 25, 2012 https://doi.org/10.3892/ijo.2012.1530
Pages: 1110-1118

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Abstract

Periostin (PN) is mainly produced from stromal fibroblasts in cholangiocarcinoma (CCA) and shows strong impact in cancer promotion. This work aimed to investigate the mechanism that PN uses to drive CCA invasion. It was found that ITGα5β1 and α6β4 showed high expression in non-tumorigenic biliary epithelial cells and in almost all CCA cell lines. PN had preferential binding to CCA cells via ITGα5β1 and blocking this receptor by either neutralizing antibody or siITGα5 could attenuate PN-induced invasion. After PN-ITGα5β1 binding, intracellular pAKT was upregulated whereas there was no change in pERK. Moreover, PN could not activate AKT in condition of treatment with a PI3K inhibitor. These data provide evidence that PN-activated invasion of CCA cells is through the ITGα5β1/PI3K/AKT pathway. Strategies aimed to inhibit this pathway may, thus, provide therapeutic benefits.

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