The Scribble Cell Polarity Module in the Regulation of Cell Signaling in Tissue Development and Tumorigenesis

Rebecca Stephens; Krystle Lim; Marta Portela; Marc Kvansakul; Patrick O Humbert; Helena E Richardson

doi:10.1016/j.jmb.2018.01.011

The Scribble Cell Polarity Module in the Regulation of Cell Signaling in Tissue Development and Tumorigenesis

J Mol Biol. 2018 Sep 28;430(19):3585-3612. doi: 10.1016/j.jmb.2018.01.011. Epub 2018 Feb 8.

Authors

Rebecca Stephens¹, Krystle Lim¹, Marta Portela², Marc Kvansakul¹, Patrick O Humbert³, Helena E Richardson⁴

Affiliations

¹ Department of Biochemistry and Genetics, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
² Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute (CSIC), Avenida Doctor Arce, 37, Madrid 28002, Spain.
³ Department of Biochemistry and Genetics, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Victoria, Australia; Department of Biochemistry & Molecular Biology, University of Melbourne, Melbourne, Victoria 3010, Australia; Department of Pathology, University of Melbourne, Melbourne, Victoria 3010, Australia.
⁴ Department of Biochemistry and Genetics, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Victoria, Australia; Department of Biochemistry & Molecular Biology, University of Melbourne, Melbourne, Victoria 3010, Australia; Department of Anatomy & Neurobiology, University of Melbourne, Melbourne, Victoria 3010, Australia. Electronic address: h.richardson@latrobe.edu.au.

PMID: 29409995
DOI: 10.1016/j.jmb.2018.01.011

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.

Keywords: Cell polarity; Cell signaling; Protein interactions; Scribble module; Tumourigenesis.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Biomarkers*
Cell Polarity / physiology*
Cell Transformation, Neoplastic*
Gene Expression Regulation
Humans
Organ Specificity
Organogenesis*
Signal Transduction*
Structure-Activity Relationship

Substances

Biomarkers