title: EVA1A inhibits GBM cell proliferation by inducing autophagy and apoptosis.
abstract: Eva-1 homolog A (EVA1A) is a novel lysosome and endoplasmic reticulum-associated protein involved in autophagy and apoptosis. In this study, we constructed a recombinant adenovirus 5-EVA1A vector (Ad5-EVA1A) to overexpress EVA1A in glioblastoma (GBM) cell lines and evaluated its anti-tumor activities in vitro and in vivo. We found that overexpression of EVA1A in three GBM cell lines (U251, U87 and SHG44) resulted in a suppression of tumor cell growth via activation of autophagy and induction of cell apoptosis in a dose- and time-dependent manner. EVA1A-mediated autophagy was associated with inactivation of the mTOR/RPS6KB1 signaling pathway. Furthermore in vivo, overexpression of EVA1A successfully inhibited tumor growth in NOD/SCID mice. Our data suggest that EVA1A-induced autophagy and apoptosis play a role in suppressing the development of GBM and their up-regulation may be an effective method for treating this form of cancer.
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Kan
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
authors.forename: Guang
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Peking University Center for Human Disease Genomics, Beijing 100191, China.
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: baiyun@bjmu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D015815:Cell Adhesion Molecules; C112474:MPZL2 protein, human; D012333:RNA, Messenger
keywords: Anti-tumor activity; Autophagy; EVA1A; GBM; Proliferation; mTOR/RPS6KB1