Disentangling gene interactions in nematodes helps us learn about human cancer

New research highlights genes that control cell division, and others that invade nearby tissues

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a stained blue roundworm against a black background

National Institutes of Health on Wikimedia Commons

The basement membrane is a thin layer of cells and molecules that divides internal or external body surfaces (like your skin or blood vessels) from connective tissue. Basement membrane invasion is when a cell “invades” or moves across neighboring tissues, and it happens a lot in cancers. While many discoveries about how this process plays a role in cancer have been made in mice and human cells, these studies can take a long time. The nematode Caenorhabditis elegans (C. elegans) is a great alternative because it can quickly reproduce and actually uses basement membrane invasion to make its vulva.

Previous work has found that four genes are needed for basement membrane invasion in C. elegans. However, until now it wasn’t clear how these four genes interacted with each other. A recent study, published in the journal Development, discovered that these genes work in a specific cell called the anchor cell (AC) prior to invasion to regulate its division.  The AC is a good cell to study because, in C. elegans, it must invade the vulval cells to form a bridge between the uterus and the nematode's vulva. If the AC does not do this, the nematode can't lay eggs.

When the four genes were individually turned off in healthy worms, instead of having one AC that could invade, they had many ACs that couldn’t invade the basement membrane, suggesting that turning off the genes prevents the AC from stopping itself from dividing. The researchers wondered if these mutations could be fixed by adding a protein called CKI-1, which is required to control cell division. Adding CKI-1 into the AC solved the problem when some combinations of the four genes were switched off, but not others, a hint that those other genes might perform different functions. But they work together to help the AC invade the vulval cells, a process which mirrors the way cancer cells invade other parts of the body.

Although these findings may sound incredibly specific and complex (and they are!), because the genomes of C. elegans are so similar to ours, they provide a roadmap for finding human genes that may be involved in cancer.