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 U87
MG
glioma cells with down‐regulation of
TGF
‐β signaling.
DCN
also activated autophagy, as indicated by monodansylcadaverine (
MDC
) staining, increase in
LC
3 I/
LC
3
II
conversion, and p62/
SQSTM
1 degradation in U87
MG
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 U87
MG
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 si
RNA
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.
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