蒋春香,郭新建

SCRIB（scribble）是一种表达于上皮细胞基底外侧的极性蛋白，对于上皮细胞极性的建立和维持具有不可或缺的作用,SCRIB在上皮肿瘤发中发挥抑癌基因作用[1]。研究显示从基底膜侧转移到细胞质中的SCRIB蛋白异常表达与肿瘤的发生相关，这种异常表达可能促进了肿瘤细胞的生长和侵袭，加速了肿瘤的发展。SCRIB作为支架蛋白影响多个细胞信号通路，参与细胞增殖，分化和迁移等过程[2]。本文就SCRIB蛋白在不同肿瘤中的作用机制及其调控细胞内信号通路进行综述。

SCRIB蛋白；信号通路；细胞极性；调控机制；综述

[1] Milgrom-Hoffman MHumbert P O.Regulation of cellular and PCP signalling by the Scribblepolarity module[J].Semin Cell Dev Biol, 2018,81:33-45. [2] Stephens R,Lim K,Portela M,et al.The Scribble Cell Polarity Module in the Regulation of CellSignaling in Tissue Development and Tumorigenesis[J].Journal of Molecular Biology,2018,430(19):3585-3612. [3] 刘毅,徐兰,方未英,等.顶-底极性复合物与癌症的关系研究进展[J].现代生物医学进展,2016,16(20):3960-3964,3973. [4] Assémat E,Bazellières E,Pallesi-Pocachard E,et al.Polarity complex proteins[J]Biochim Biophys Acta,2008,1778(3):614-630. [5] Elsum IA,Martin C,Humbert PO.Scribble regulates an EMT polarity pathway through modulation of MAPKERK signaling to mediate junction formation.J Cell Sci.2013;126:3990-99. [6] Martin-Belmonte F,Perez-Moreno M.Epithelial cell polarity,stem cells and cancer.Nat Rev Cancer.2011;12:23–38. [7] Huang L,Muthuswamy SK.Polarity protein alterations in carcinoma:a focus on emerging roles for polarity regulators.Curr Opin Genet Dev.2010;20:41-50. [8] Martin-Belmonte F,Perez-Moreno M.Epithelial cell polarity,stem cells and cancer.Nat Rev Cancer.2011;12:23-38. [9] Navarro C,Nola S,Audebert S,Santoni MJ,Arsanto JP,Ginestier C,Marchetto S,Jacquemier J,Isnardon D,Le Bivic A,Birnbaum D,Borg JP.Junctional recruitment of mammalian scribble relies on e-cadherin engagement.Oncogene.2005;24:4330-39. [10] Thiery JP,Acloque H,Huang RY,Nieto MA.Epithelialmesenchymal transitions in development and disease.Cell.2009;139:871-90. [11] Zhan L,Rosenberg A,Bergami KC,Yu M,Xuan Z,Jaffe AB,Allred C,Muthuswamy SK.Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma.Cell.2008;135:865–78. [12] Wan S,Meyer AS,Weiler SM,Rupp C,Tóth M,Sticht C,Singer S,Thomann S,Roessler S,Schorpp-Kistner M,Schmitt J,Gretz N,Angel P,et al.Cytoplasmic localization of the cell polarity factor scribble supports liver tumor formation and tumor cell invasiveness.Hepatology. 2018;67:1842-56. [13] Dow L E,Elsum I A,King C L,et al.Loss of human Scribble cooperates with H-Ras to promotecell invasion through deregulation of MAPK signalling[J].Oncogene,2008,27(46):5988-6001. [14] Li X,Yang H,Liu J,et al.Scribble-mediated membrane targeting of PHLPP1 is required for itsnegative regulation of Akt[J].EMBO Rep, 2011,12(8):818-24. [15] Cordenonsi M,Zanconato F,Azzolin L,et al.The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells[J].Cell,2011,147(4):759-72. [16] Daulat A M,Wagner M S,Walton A,et al.The Tumor Suppressor SCRIB is a Negative Modulatorof the Wnt/beta-Catenin Signaling Pathway[J].Proteomics,2019,19(21-22):e1800487. [17] 吴艳霞,姜汉国.上皮-间质转化在肿瘤侵袭转移中的作用研究进展[J].医学综述,2013,19(19):3510-3512. [18] Guarino M.Epithelial-mesenchymal transition and tumor invasion[J].Int J Biochem Cell Biol,2007,39(12):2153-2160. [19] Etienne-Manneville S.Polarity proteins in migration and invasion[J].Oncogene,2008,27(55):6970-6980. [20] Moreno-Bueno G,Portillo F,Cano A.Transcriptional regulation of cell polarity in EMT and cancer[J].Oncogene,2008,27(55):6958-6969. [21] Kapil S,Sharma BK,Patil M,et al.The cell polarity protein Scrib functions as a tumor suppressor in liver cancer[J].Oncotarget,2017, 8(16):26515-2653. [22] 赵威,李侠,岳树强,等.极性蛋白调控肿瘤发生的分子机制[J].国际肿瘤学杂志,2012,39(3):179-182. [23] Dow LE,Elsum IA,King CL,et al.Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling[J].Oncogene,2008,27(46):5988-6001. [24] Hussein UK,Ha SH,Ahmed AG,Kim KM,Park SH,Kim CY,Kwon KS,Zhang Z,Lee SA,Park HS,Park BH,Lee H,Chung MJ,Moon WS,Kang MJ,Jang KY.FAM83H and SCRIB stabilizeβ-catenin and stimulate progression of gastric carcinoma.Aging(Albany NY).2020 Jun 20;12(12):11812-11834. [25] Pearson H B,Perez-Mancera P A,Dow L E,et al.SCRIB expression is deregulated in humanprostate cancer,and its deficiency in mice promotes prostate neoplasia[J].J Clin Invest,2011,121(11):4257-67. [26] Elsum I A,Yates L L,Pearson H B,et al.Scrib heterozygosity predisposes to lung cancer andcooperates with KRas hyperactivation to accelerate lung cancer progression in vivo[J].Oncogene,2014,33(48):5523-33. [27] Pearson H B,Perez-Mancera P A,Dow L E,et al.SCRIB expression is deregulated in humanprostate cancer,and its deficiency in mice promotes prostate neoplasia[J].J Clin Invest,2011,121(11):4257-67. [28] Zhan L,Rosenberg A,Bergami K C,et al.Deregulation of Scribble Promotes MammaryTumorigenesis and Reveals a Role for Cell Polarity in Carcinoma[J].Cell,2008,135(5):865-878. [29] Godde N J,Sheridan J M,Smith L K,et al.Scribble modulates the MAPK/Fra1 pathway todisrupt luminal and ductal integrity and suppress tumour formation in the mammary gland[J].PLoS Genet,2014,10(5):e1004323. [30] Shen H,Huang C,Wu J,Li J,Hu T,Wang Z,Zhang H,Shao Y,Fu Z.SCRIB Promotes Proliferation and Metastasis by Targeting Hippo/ YAP Signalling in Colorectal Cancer.Front Cell Dev Biol.2021 Apr 15;9:656359.

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