How ADAMTS5, driven by Rab25, helps ovarian cancer cells spread

What is it about?

Ovarian cancer is the third most common cancer of the female reproductive system, and survival rates drop below 30% once the cancer spreads to other parts of the body. For cancer to spread, it has to break down and move through the tissue around it, a process often driven by proteins called proteases. One of these proteases, called ADAMTS5, is found at higher levels in aggressive ovarian tumors compared to less dangerous ones, suggesting it helps cancer spread. Another protein, Rab25, appears to “switch on” ADAMTS5 through a signaling pathway in the cell. In our research, we found that Rab25 increases ADAMTS5, which in turn makes ovarian cancer cells more able to move and invade their surroundings. Blocking ADAMTS5 stopped cancer cells from spreading in lab-grown 3D tumor models. In patient samples, higher ADAMTS5 levels were linked with worse outcomes. This means ADAMTS5 could be an important new target for treatments designed to stop ovarian cancer from spreading.

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Photo by Visax on Unsplash

Photo by Visax on Unsplash

Why is it important?

Studying the mechanisms that control ovarian cancer metastasis is crucial because most women are diagnosed at advanced stages, when the cancer has already spread beyond the ovaries. This spread, rather than the original tumor itself, is the main cause of poor survival, with fewer than one in three patients living five years after diagnosis once metastasis occurs. By understanding the molecular and cellular processes that allow ovarian cancer cells to invade surrounding tissues and establish new tumours, we aim at identifying weak points in the cancer’s progression. These insights could lead to the development of new therapies that specifically block metastasis, improve patient survival, and reduce the burden of this aggressive disease.

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