title: Overexpression of RACK1 Promotes Metastasis by Enhancing Epithelial-Mesenchymal Transition and Predicts Poor Prognosis in Human Glioma.
abstract: Emerging studies show that dysregulation of the receptor of activated protein kinase C1 (RACK1) plays a crucial role in tumorigenesis and progression of various cancers. However, the biological function and underlying mechanism of RACK1 in glioma remains poorly defined. Here, we found that RACK1 was significantly up-regulated in glioma tissues compared with normal brain tissues, being closely related to clinical stage of glioma both in mRNA and protein levels. Moreover, Kaplan-Meier analysis demonstrated that patients with high RACK1 expression had a poor prognosis (p= 0.0062, HR = 1.898, 95% CI: 1.225-3.203). In vitro functional assays indicated that silencing of RACK1 could dramatically promote apoptosis and inhibit cell proliferation, migration, and invasion of glioma cells. More importantly, knockdown of RACK1 led to a vast accumulation of cells in G0/G1 phase and their reduced proportions at the S phase by suppressing the expression of G1/S transition key regulators Cyclin D1 and CDK6. Additionally, this forced down-regulation of RACK1 significantly suppressed migration and invasion via inhibiting the epithelial-mesenchymal transition (EMT) markers, such as MMP2, MMP9, ZEB1, N-Cadherin, and Integrin-β1. Collectively, our study revealed that RACK1 might act as a valuable prognostic biomarker and potential therapeutic target for glioma.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. lvqiaoli2008@sina.com.|Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China. lvqiaoli2008@sina.com.
authors.forename: Qiao-Li
authors.initials: QL
authors.lastname: Lv
authors.affiliation: Department of Neurology, The Brain Hospital of Hunan Province, Changsha 410008, China. m13397602527@163.com.
authors.forename: Yuan-Tao
authors.initials: YT
authors.lastname: Huang
authors.affiliation: Department of Oncology, Changsha Central Hospital, Changsha 410008, China. zhuifenglang12@126.com.
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. 13487569804@163.com.|Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China. 13487569804@163.com.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. guoying198688@163.com.|Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China. guoying198688@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China. quqiang1983@sina.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Qu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. scy_csu2016@163.com.|Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China. scy_csu2016@163.com.
authors.forename: Bao
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. hu773589905@163.com.|Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China. hu773589905@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510275, China. kjade.cheng@hotmail.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Oncology, Changsha Central Hospital, Changsha 410008, China. hhzhou2003@sina.com.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. chenshuhui2008@126.com.|Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China. chenshuhui2008@126.com.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005910:Glioma / Q000503:physiopathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D010455:Peptides / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D015854:Up-Regulation
chemical_list: C530104:CCND1 protein, human; D010455:Peptides; D012333:RNA, Messenger; D000075370:Receptors for Activated C Kinase; D019938:Cyclin D1; C070301:peptide I; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: RACK1; cell cycle; epithelial-mesenchymal transition; prognosis