Decorin Suppresses Invasion and EMT Phenotype of Glioma by Inducing Autophagy via c-Met/Akt/mTOR Axis.

Yanfei Jia,Xiaodong Luo,Qiang Yang,Qian Feng,Hu Yang,Bo Tang,Qiang Li

doi:10.3389/fonc.2021.659353

Yanfei Jia, Xiaodong Luo + Show 5 more

Open Access

https://doi.org/10.3389/fonc.2021.659353

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Abstract

Decorin exhibits inhibitory effects in tumorigenesis in various types of cancers. The clinical characteristics of 42 patients with GBM were reviewed and analyzed. Lentiviral constructs for decorin overexpression and shRNA-mediated silencing were established for U87MG cells and T98G cells, respectively. The expressions of EMT- and autophagy-associated markers were detected in GBM cell lines. The migration and invasion of the glioma cells were assayed to reflect the malignant behavior of GBM. A mouse xenograft model was used to verify the effect of decorin on autophagy in vivo. Reduced expression of decorin in glioma tissues was associated with a poor survival of the patients. Decorin overexpression suppressed cell migration, invasion and attenuated EMT phenotype in glioma cell lines. Further study indicated that decorin inhibited EMT phenotype through the induction of autophagy. The mechanisms include inhibiting the activation of c-Met/Akt/mTOR signaling and regulating the expressions of mesenchymal markers including Slug, vimentin and Twist, and epithelial marker E-cadherin. In addition, decorin overexpression in a mice model can also suppress the GBM invasion and EMT phenotype. In conclusion, decorin suppresses invasion and EMT phenotype of glioma by inducing autophagy via c-Met/Akt/mTOR axis.

Highlights

Glioblastoma multiforme (GBM) is one of the deadliest malignant tumors that occurs in the central nervous system [1]
We investigated the role of decorin in autophagy and epithelial to mesenchymal transition (EMT) in GBM, and revealed a molecular mechanism of its inhibitory effects on the malignant behavior of GBM
Decorin, which belongs to the small leucine-rich proteoglycan (SLRP) family, is a key component of extracellular matrix (ECM) structure and function

Summary

Introduction

Glioblastoma multiforme (GBM) is one of the deadliest malignant tumors that occurs in the central nervous system [1]. The epithelial to mesenchymal transition (EMT), a crucial biological process associated with embryonic and post-natal development, has been reported to regulate tumor aggressive invasion and metastasis in multiple tumors [3, 4], Decorin vs Glioma including gliomas [5, 6]. In GBM, multiple EMT activators including ZEB1 could induce glioma cells to acquire pseudopodia and higher invasive ability, which are special features of the mesenchymal cells [7]. EMT may initiate the dedifferentiation of the cells, allowing the cells to obtain malignant characteristics including tumor invasive ability and multidrug resistance [8, 9]. The exact effects of autophagy on the EMT in GBM remain unknown

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