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Published on: November 2, 2020
[hScrib: a potential novel tumor suppressor]
1Laboratoire de Pharmacologie Moléculaire, U119 Inserm, Institut Paoli-Calmettes, 27, boulevard Leï-Roure, 13009 Marseille, France. borg@marseille.inserm.fr
Abstract:
Establishment and maintenance of epithelial cell polarity rely on finely tuned protein networks comprising cell surface molecules, cytoplasmic adaptors, and enzymes connected to the actin cytoskeleton. Oncogenes and tumor suppressors promote cell proliferation and resistance to apoptosis and, in many cases, alter some of these molecular scaffolds, and profoundly affect the epithelial cytoarchitecture. Reciprocally, loss of central actors of epithelial polarity unleashes normally repressed signaling pathways and perturb the shape and functions of epithelial tissues. Among the newcomers impacting on epithelial integrity, Scribble is a scaffold protein of a remarkable importance that furthermore displays a tumor suppressing activity in Drosophila melanogaster. Together with Discs Large (Dlg) and Lethal Giant Larvae (Lgl), two known tumor suppressors, Scribble acts on the correct positioning of epithelial junctions required to organize functional epithelial sheets. Scribble, Dlg and Lgl proteins are well conserved during evolution at the molecular and subcellular level implying their potential role in cell polarity and tumorigenesis in humans. Recent findings on hScrib, the human orthologue of Scribble, are discussed here.
Insights
Epithelial cell polarity is crucial for tissue function and is regulated by proteins like Scribble. Loss of Scribble disrupts polarity and can lead to tumor development, highlighting its tumor suppressor role.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Context:
- Epithelial cell polarity is maintained by complex protein networks.
- Oncogenes and tumor suppressors impact epithelial architecture and function.
- Disruption of polarity can activate repressed signaling pathways.
Purpose:
- To discuss the role of the scaffold protein Scribble in maintaining epithelial integrity.
- To highlight Scribble's tumor suppressor activity in Drosophila melanogaster.
- To explore the evolutionary conservation and potential human relevance of Scribble, Discs Large (Dlg), and Lethal Giant Larvae (Lgl) proteins in cell polarity and tumorigenesis.
Summary:
- Scribble, along with Dlg and Lgl, are key tumor suppressors involved in epithelial junction positioning and functional epithelial sheet organization.
- These proteins are evolutionarily conserved, suggesting a conserved role in cell polarity and human tumorigenesis.
- Recent findings on the human orthologue, hScrib, are presented.
Impact:
- Understanding Scribble's function provides insights into epithelial tissue organization and cancer development.
- Identifying key regulators of cell polarity can lead to novel therapeutic strategies for epithelial cancers.
- The study underscores the link between fundamental cell polarity mechanisms and oncogenic processes.
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