APC-driven actin nucleation powers collective cell dynamics in colorectal cancer cells

Baró, Lautaro; Islam, Asifa; Brown, Hannah; Bell, Zoë A.; Juanes, M. Angeles

doi:10.1016/j.isci.2023.106583

Cited by 5 publications

(1 citation statement)

References 65 publications

(99 reference statements)

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“…Tumor cells are characterized by highly invasive and enhanced actin polymerization activity and an aberrant expression of actin-regulating proteins [ 60 , 61 ]. It was demonstrated that the tumor suppressor adenomatous polyposis coli-dependent actin contributes to maintaining F-actin levels, as well as E-cadherin and Occludin at cell junctions [ 62 ]. Actin cytoskeleton is used as a therapeutic target in tumor motility through the pharmacological inhibition of actin assembly.…”

Section: Discussionmentioning

confidence: 99%

Actin Cytoskeleton Polymerization and Focal Adhesion as Important Factors in the Pathomechanism and Potential Targets of Mucopolysaccharidosis Treatment

Gaffke

Rintz

Pierzynowska

et al. 2023

Cells

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The main approach used in the current therapy of mucopolysaccharidosis (MPS) is to reduce the levels of glycosaminoglycans (GAGs) in cells, the deposits considered to be the main cause of the disease. Previous studies have revealed significant differences in the expression of genes encoding proteins involved in many processes, like those related to actin filaments, in MPS cells. Since the regulation of actin filaments is essential for the intracellular transport of specific molecules, the process which may affect the course of MPSs, the aim of this study was to evaluate the changes that occur in the actin cytoskeleton and focal adhesion in cells derived from patients with this disease, as well as in the MPS I mouse model, and to assess whether they could be potential therapeutic targets for different MPS types. Western-blotting, flow cytometry and transcriptomic analyses were employed to address these issues. The levels of the key proteins involved in the studied processes, before and after specific treatment, were assessed. We have also analyzed transcripts whose levels were significantly altered in MPS cells. We identified genes whose expressions were changed in the majority of MPS types and those with particularly highly altered expression. For the first time, significant changes in the expression of genes involved in the actin cytoskeleton structure/functions were revealed which may be considered as an additional element in the pathogenesis of MPSs. Our results suggest the possibility of using the actin cytoskeleton as a potential target in therapeutic approaches for this disease.

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Section: Discussionmentioning

confidence: 99%

Actin Cytoskeleton Polymerization and Focal Adhesion as Important Factors in the Pathomechanism and Potential Targets of Mucopolysaccharidosis Treatment

Gaffke

Rintz

Pierzynowska

et al. 2023

Cells

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A truncation mutant of adenomatous polyposis coli impairs apical cell extrusion through elevated epithelial tissue tension

Gan,

Giri,

Begun

et al. 2024

Cytoskeleton

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Tissue tension encompasses the mechanical forces exerted on solid tissues within animal bodies, originating from various sources such as cellular contractility, interactions with neighboring cells and the extracellular matrix. Emerging evidence indicates that an imbalance in such forces can influence structural organization, homeostasis, and potentially contribute to disease. For instance, heightened tissue tension can impede apical cell extrusion, leading to the retention of apoptotic or transformed cells. In this study, we investigate the potential role of adenomatous polyposis coli (APC) in modulating tissue tension. Our findings reveal that expression of an APC truncation mutant elevates epithelial tension via the RhoA/ROCK pathway. This elevation induces morphological alterations and hampers apoptotic cell extrusion in cultured epithelial cells and organoids, both of which could be mitigated by pharmacologically restoring the tissue tension. This raises the possibility that APC mutations may exert pathogenetic effects by altering tissue mechanics.

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Tumor invasiveness is regulated by the concerted function of APC, formins, and Arp2/3 complex

Baro,

Almhassneh,

Islam

et al. 2024

iScience

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APC-driven actin nucleation powers collective cell dynamics in colorectal cancer cells

Cited by 5 publications

References 65 publications

Actin Cytoskeleton Polymerization and Focal Adhesion as Important Factors in the Pathomechanism and Potential Targets of Mucopolysaccharidosis Treatment

Actin Cytoskeleton Polymerization and Focal Adhesion as Important Factors in the Pathomechanism and Potential Targets of Mucopolysaccharidosis Treatment

A truncation mutant of adenomatous polyposis coli impairs apical cell extrusion through elevated epithelial tissue tension

Tumor invasiveness is regulated by the concerted function of APC, formins, and Arp2/3 complex

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