title: AEG-1/MTDH-activated autophagy enhances human malignant glioma susceptibility to TGF-β1-triggered epithelial-mesenchymal transition.
abstract: Autophagy is a tightly regulated process activated in response to metabolic stress and other microenvironmental changes. Astrocyte elevated gene 1 (AEG-1) reportedly induces protective autophagy. Our results indicate that AEG-1 also enhances the susceptibility of malignant glioma cells to TGF-β1-triggered epithelial-mesenchymal transition (EMT) through induction of autophagy. TGF-β1 induced autophagy and activated AEG-1 via Smad2/3 phosphorylation in malignant glioma cells. Also increased was oncogene cyclin D1 and EMT markers, which promoted tumor progression. Inhibition of autophagy using siRNA-BECN1 and siRNA-AEG-1 suppressed EMT. In tumor samples from patients with malignant glioma, immunohistochemical assays showed that expression levels of TGF-β1, AEG-1, and markers of autophagy and EMT, all gradually increase with glioblastoma progression. In vivo siRNA-AEG-1 administration to rats implanted with C6 glioma cells inhibited tumor growth and increased the incidence of apoptosis among tumor cells. These findings shed light on the mechanisms underlying the invasiveness and progression of malignant gliomas.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zou
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Breast Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Ou
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xuguan
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
authors.forename: Zhongchang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Medical School of Nanjing University, Nanjing 210093, China.
authors.forename: Aiqin
authors.initials: A
authors.lastname: Jiang
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, School of Laboratory Medicine, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Kunmei
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Anatomy, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ni
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Sulan
authors.initials: S
authors.lastname: Zhai
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xuerong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
mesh_terms: D000818:Animals; D001343:Autophagy; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D053773:Transforming Growth Factor beta1
keywords: astrocyte elevated gene-1; epithelial mesenchymal transition; malignant glioma invasion; protective autophagy; transforming growth factor-β1