title: Decorin-mediated inhibition of the migration of U87MG glioma cells involves activation of autophagy and suppression of TGF-β signaling.
abstract: Decorin (DCN) is a major member of the small leucine-rich proteoglycan (SLRP) family that is critically involved in tumorigenesis and the development of metastasis of cancers, including glioma. Overexpression of DCN was indicated to suppress glioma cell growth. However, the role of DCN in the migration of glioma cells remain elusive. In this study, we found that treatment with exogenous DCN inhibited the adhesion and migration of U87MG glioma cells with down-regulation of TGF-β signaling. DCN also activated autophagy, as indicated by monodansylcadaverine (MDC) staining, increase in LC3 I/LC3 II conversion, and p62/SQSTM1 degradation in U87MG cells. The increased activity of autophagy was found to be connected to the inhibition on glioma cell migration. Knockdown of DCN expression or the disruption of autophagy with 3-methyladenine (3-MA) was able to reduce the suppression on cell adhesion and migration induced by DCN. When U87MG cells were treated with temozolomide (TMZ), induction of autophagy and up-regulation of DCN were observed, accompanied by suppressed cell adhesion and migration. Transfection of siRNA targeting DCN attenuated the suppressive effect of TMZ on glioma cell migration and adhesion. Our results indicated that the migration of glioma cells was under the control of the active status of autophagy, with DCN serving as a key player, as well as an indicator of the outcome. Therefore, it is suggested that autophagy-modulating reagents could be considered for the treatment of invasive glioma.
authors.affiliation: Department of Medical Genetics and Developmental Biology Capital Medical University Beijing China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yao
authors.affiliation: Department of Biochemistry and Molecular Biology Capital Medical University Beijing China; Beijing Key Laboratory for Researches in Cancer Invasion and Metastasis Cancer Institute of Capital Medical University Beijing China.
authors.forename: Chen-Guang
authors.initials: CG
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology Capital Medical University Beijing China.
authors.forename: Ming-Tao
authors.initials: MT
authors.lastname: Gong
authors.affiliation: Department of Medical Genetics and Developmental Biology Capital Medical University Beijing China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery Beijing Tiantan Hospital China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology Capital Medical University Beijing China; Beijing Key Laboratory for Researches in Cancer Invasion and Metastasis Cancer Institute of Capital Medical University Beijing China; Beijing Institute of Brain Disorders China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
keywords: TGF‐β signal; autophagy; decorin; glioma; migration