Periostin activates integrin α5β1 through a PI3K/AKT‑dependent pathway in invasion of cholangiocarcinoma.
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.
Department of Biochemistry, Faculty of Medicine, Khon Kaen University,                     Khon Kaen, Thailand.
Kusumawadee
K
Utispan
Jumaporn
J
Sonongbua
Peti
P
Thuwajit
Siri
S
Chau-In
Chawalit
C
Pairojkul
Sopit
S
Wongkham
Chanitra
C
Thuwajit
D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology; D001650:Bile Duct Neoplasms / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering
D019138:Antibodies, Blocking; D015815:Cell Adhesion Molecules; D039081:Integrin alpha5beta1; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; C512835:POSTN protein, human