The Scribble Cell Polarity Module in the Regulation of Cell Signaling in Tissue Development and Tumorigenesis. Issue 19 (28th September 2018)

• Record Type: Journal Article
• Authors: Stephens, Rebecca; Lim, Krystle; Portela, Marta; Kvansakul, Marc; Humbert, Patrick O.; Richardson, Helena E.
• Is Part Of: Journal of molecular biology. Volume 430:Issue 19(2018)
• Page Start: 3585
• Page End: 3612
• Publication Date: 2018-09-28
• Subjects: Cell polarity -- Scribble module -- Protein interactions -- Cell signaling -- Tumourigenesis; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2018.01.011
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: The Scribble cell polarity module, comprising Scribbled (Scrib), Discs-large (Dlg) and Lethal-2-giant larvae (Lgl), has a tumor suppressive role in mammalian epithelial cancers. The Scribble module proteins play key functions in the establishment and maintenance of different modes of cell polarity, as well as in the control of tissue growth, differentiation and directed cell migration, and therefore are major regulators of tissue development and homeostasis. Whilst molecular details are known regarding the roles of Scribble module proteins in cell polarity regulation, their precise mode of action in the regulation of other key cellular processes remains enigmatic. An accumulating body of evidence indicates that Scribble module proteins play scaffolding roles in the control of various signaling pathways, which are linked to the control of tissue growth, differentiation and cell migration. Multiple Scrib, Dlg and Lgl interacting proteins have been discovered, which are involved in diverse processes, however many function in the regulation of cellular signaling. Herein, we review the components of the Scrib, Dlg and Lgl protein interactomes, and focus on the mechanism by which they regulate cellular signaling pathways in metazoans, and how their disruption leads to cancer. Graphical Abstract: Highlights: The Scribble cell polarity module has a tumor suppressive role in mammalian epithelial cancers Scribble module proteins interact with many signaling proteins Scribble module proteins control signaling pathways, which are linked to the control of tissue growth, differentiation and cell migration Understanding the molecular interactions between Scribble module proteins and their interacting partners will increase our understanding of their role in tumorigenesis