Amoeboid-mesenchymal transition and the proteolytic control of cancer invasion plasticity - PubMed
3 hours ago
- #proteolysis
- #MMP14
- #cancer invasion
- The study investigates invasion plasticity in cancer cells, which can switch between collective, mesenchymal, and amoeboid invasion phenotypes.
- Contrary to current belief, both mesenchymal and amoeboid invasion involve active ECM tunneling with expression of matrix-degrading metalloproteinases, particularly MMP14/MT1-MMP.
- Targeting MMP14 using CRISPR/Cas9 ablates invasive activity and co-regulates cancer cell transcriptional programs, and this requirement is not restored by factors like matrix changes or cancer-associated fibroblasts.
- In low-density collagen hydrogels, MMP14-deleted cells can invade but suffer nuclear envelope and DNA damage, indicating MMP14's role in maintaining nuclear integrity during invasion.
- In human breast tissue explants, MMP14 is again essential for invasive activity, and spatial transcriptomic analyses of human breast cancers show MMP14 expression in infiltrating cells near proteolyzed collagen fragments, highlighting its pathophysiological importance.