Open AccessPeriostin regulates autophagy through integrin α5β1 or α6β4 and an AKT‐dependent pathway in colorectal cancer cell migration
Author(s) -
Thongchot Suyanee,
Singsuksawat Ekapot,
Sumransub Nuttavut,
Pongpaibul Ananya,
Trakarnsanga Attaporn,
Thuwajit Peti,
Thuwajit Chanitra
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15756
Subject(s) - periostin , autophagy , cancer research , colorectal cancer , pi3k/akt/mtor pathway , protein kinase b , cell migration , integrin , cell , chemistry , cancer , signal transduction , medicine , biology , microbiology and biotechnology , apoptosis , biochemistry , extracellular matrix
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 si ITGα5 ‐treated HT‐29 and si ITGβ4 ‐treated HCT‐116 CRC cells attenuated epithelial‐to‐mesenchymal transitions (EMT)‐related genes and pAKT compared with those in si ITG ‐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.