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Title: Periostin regulates autophagy through integrin α5β1 or α6β4 and an AKT-dependent pathway in colorectal cancer cell migration
Authors: Suyanee Thongchot
Ekapot Singsuksawat
Nuttavut Sumransub
Ananya Pongpaibul
Attaporn Trakarnsanga
Peti Thuwajit
Chanitra Thuwajit
Faculty of Medicine, Siriraj Hospital, Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jan-2020
Citation: Journal of Cellular and Molecular Medicine. (2020)
Abstract: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd Colorectal cancer (CRC) is one of the most fatal cancers with highly invasive properties. The progression of CRC is determined by the driving force of periostin (PN) from cancer-associated fibroblasts (CAFs) in the tumour microenvironment. This present work aims to investigate autophagy-mediated CRC invasion via the receptor integrin (ITG) by PN. The level of PN in 410 clinical CRC tissues was found increased and was an independent poor prognosis marker (HR = 2.578, 95% CI = 1.218-5.457, P-value =.013) with a significant correlation with overall survival time (P-value <.001). PN activated proliferation, migration and invasion of CRC cells, but with reduced autophagy. Interestingly, the reduction of LC3 autophagic protein corresponded to the increased ability of CRC cell migration. The siITGα5-treated HT-29 and siITGβ4-treated HCT-116 CRC cells attenuated epithelial-to-mesenchymal transitions (EMT)-related genes and pAKT compared with those in siITG-untreated cells. The reduction of pAKT by a PI3K inhibitor significantly restored autophagy in CRC cells. These evidences confirmed the effect of PN through either ITGα5β1 or ITGα6β4 and the AKT-dependent pathway to control autophagy-regulated cell migration. In conclusion, these results exhibited the impact of PN activation of ITGα5β1 or ITGα6β4 through pAKT in autophagy-mediated EMT and migration in CRC cells.
ISSN: 15821838
Appears in Collections:Scopus 2020

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