AI Article Synopsis
- Epithelial adherens junctions (AJs) are cell-cell adhesion complexes that not only respond to tissue mechanics but also impact the extracellular matrix (ECM).
- Researchers discovered that the AJ component PLEKHA7 controls ECM remodeling by regulating key components MMP1 and LOX through specific miRNAs in colon epithelial cells.
- When PLEKHA7 is depleted, cells experience altered ECM remodeling, increased migration and invasion, and abnormal colony formations in stiffer environments, which may relate to disease processes like fibrosis and cancer.
Article Abstract
Epithelial adherens junctions (AJs) are cell-cell adhesion complexes that are influenced by tissue mechanics, such as those emanating from the extracellular matrix (ECM). Here, we introduce a mechanism whereby epithelial AJs can also regulate the ECM. We show that the AJ component PLEKHA7 regulates levels and activity of the key ECM remodeling components MMP1 and LOX in well-differentiated colon epithelial cells, through the miR-24 and miR-30c miRNAs. PLEKHA7 depletion in epithelial cells results in LOX-dependent ECM remodeling in culture and in the colonic mucosal lamina propria in mice. Furthermore, PLEKHA7-depleted cells exhibit increased migration and invasion rates that are MMP1- and LOX- dependent, and form colonies in 3D cultures that are larger in size and acquire aberrant morphologies in stiffer matrices. These results reveal an AJ-mediated mechanism, through which epithelial cells drive ECM remodeling to modulate their behavior, including acquisition of phenotypes that are hallmarks of conditions such as fibrosis and tumorigenesis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160653 | PMC |
| http://dx.doi.org/10.1101/2024.05.28.596237 | DOI Listing |
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