Extracellular forces help epithelial cells stick together

Extracellular forces help epithelial cells stick together

Different surfaces and organs of the body are covered by epithelial tissue, which is composed of cells tightly connected to each other. The cells can be attached through junctions that are in direct contact with the cytoskeletal network inside the cells.

This network, composed of actin and myosin proteins that together form contractile actomyosin bundles, maintain the epithelial cells close to each other.

Recent studies have shown that physical alterations in the growth environment of cells have a significant impact on tissue function. Therefore, such changes are also connected to the onset of a number of diseases, including cancer.

Now, a research group has found that extracellular forces regulate the formation of epithelia-integrating actomyosin bundles.

"Contacts between neighboring epithelial cells generate mechanical tension, which activates a certain intracellular signalling pathway. This, in turn, drives the assembly of epithelial actomyosin structures. If components involved in the signalling pathway are disturbed, epithelial cells are detached from each other and become mobile," says the senior author.

The study utilized breast and kidney epithelial cell lines, but the researchers assume that the same mechanisms also apply to other types of epithelial cells.

Importantly, the authors find that assembly and maintenance of peripheral actomyosin bundles are dependent on the mechanosensitive CaMKK2/AMPK signaling pathway and that inhibition of this route leads to disruption of tensionmaintaining actomyosin bundles and re-growth of stress fiber precursors. This results in redistribution of cellular forces, defects in monolayer integrity, and loss of epithelial identity.

These data provide evidence that the mechanosensitive CaMKK2/AMPK pathway is critical for the maintenance of peripheral actomyosin bundles and thus dictates cell-cell junctions through cellular force distribution.

"Another important factor is that, in the case of cancer, the proteins associated with this signalling pathway that is sensitive to mechanical tension are regulated erroneously. In other words, our findings have a direct association with means that cancer cells may use to break away from the area of the original tumor, enabling them to scatter to healthy tissues," says the principal author of the article.