Rhoj Is a Novel Target for Progression and Invasion of Glioblastoma by Impairing Cytoskeleton Dynamics
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ORIGINAL ARTICLE
Rhoj Is a Novel Target for Progression and Invasion of Glioblastoma by Impairing Cytoskeleton Dynamics Mei Wang 1,2 & Xiaochun Jiang 3 & Yongbo Yang 4 & Hongjin Chen 2 & Chengfei Zhang 2 & Haojun Xu 2 & Bin Qi 5 & Chengyun Yao 6 & Hongping Xia 1,2,3,6
# The American Society for Experimental NeuroTherapeutics, Inc. 2020
Abstract Rho GTPase family members were identified as critical regulators of cell morphology, actin cytoskeleton organization, cell movement, and cell cycle and also contributed to tumor progression, which have been implicated in various types of cancer metastasis and growth. Here, we firstly reported the dysregulation of Rhoj in glioblastoma multiforme (GBM) and aimed to investigate the role and mechanism of Rhoj in GBM. We analyzed the expression of 21 Rho GTPases family members and validated the expression of Rhoj in GBM by immunohistochemistry. We further investigated the role and mechanism of Rhoj in GBM both in vitro and in vivo. We observed that Rhoj is significantly overexpressed in GBM and associated with patients’ survival. However, the role and underlying molecular mechanism of Rhoj in GBM are still unclear. We demonstrated that transcription factor c-Jun regulated the expression of Rhoj, and Rhoj interacted with moesin to promote GBM cell proliferation and migration by potentiating the activation of Rac1/PAK pathway and cytoskeletal dynamics. Rhoj may promote migration and invasion of GBM cells by regulating epithelial-mesenchymal transition (EMT)-like process. In conclusion, the Rhoj/Rac1/PAK signaling mediates invasion and progression of GBM and is a potential therapeutic target for GBM treatment. Rhoj may also be a promising biomarker for GBM diagnosis and prognosis. Key Words Rhoj . GBM . actin cytoskeleton . invasion . moesin
Introduction Glioblastoma multiforme (GBM) is a common malignant adult primary brain tumor in the central nervous system
(CNS) and is a lethal malignant tumor characterized by rapid cell division, proliferation, and unparalleled invasion with concomitant neovascularization [1]. Over the past decade, several large, publicly molecular studies demonstrated that
Mei Wang, Xiaochun Jiang and Yongbo Yang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13311-020-00910-w) contains supplementary material, which is available to authorized users. * Chengyun Yao [email protected] * Hongping Xia [email protected] 1
2
Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing 210009, China Department of Pathology, School of Basic Medical Sciences & Sir Run Run Hospital & State Key Laboratory of Reproductive Medicine & Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing 211166, China
3
Department of Neurosurgery, Yijishan Hospital of Wannan Medical College, Wuhu 241001, China
4
Department of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing 210008, Chi
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