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Periostin regulates autophagy through integrin α5β1 or α6β4 and an AKT-dependent pathway in colorectal cancer cell migration.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2020 Nov; Vol. 24 (21), pp. 12421-12432. Date of Electronic Publication: 2020 Sep 29. - Publication Year :
- 2020
-
Abstract
- 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.<br /> (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Subjects :
- Aged
Autophagy
Cell Line, Tumor
Cell Movement
Cell Proliferation
Epithelial-Mesenchymal Transition
Female
Gene Expression Regulation, Neoplastic
HCT116 Cells
Humans
Male
Middle Aged
Neoplasm Invasiveness
Phosphatidylinositol 3-Kinases metabolism
Prognosis
Proportional Hazards Models
Protein Kinase Inhibitors pharmacology
Treatment Outcome
Cell Adhesion Molecules metabolism
Colorectal Neoplasms metabolism
Integrin alpha6 metabolism
Integrin beta1 metabolism
Integrin beta4 metabolism
Integrins metabolism
Proto-Oncogene Proteins c-akt metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 24
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 32990415
- Full Text :
- https://doi.org/10.1111/jcmm.15756