Eating matrix components stimulate cancer cell migration and invasion

What is it about?

Cancer cells interact with their surroundings, known as the extracellular matrix, to grow and spread. While it is known how cancer cells break down the matrix externally, less is known about how they take it in and how this affects their movement and spread. This study found that invasive breast cancer cells internalise more more, which might help them become more aggressive. To study this process, the team developed a new method using live-cell imaging and automated tools to track matrix uptake. They discovered that proteins MAP3K1, MAPK11 (p38β), PPP2R1A, and the sodium/proton exchanger NHE1 play key roles in helping cells internalise the matrix. This process is mediated by a specific type of uptake called macropinocytosis, guided by α2β1 integrin, a molecule on the cell surface that binds to matrix components. Disrupting these proteins significantly reduced cancer cell movement and invasion in lab models. The study also showed that higher levels of α2β1 integrin and MAP3K1 were linked to worse outcomes in pancreatic cancer patients and to resistance to chemotherapy in breast cancer patients. These findings highlight a new pathway, the α2β1 integrin/p38 axis, that helps cancer cells invade and spread, offering potential targets for future treatments.

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Photo by National Cancer Institute on Unsplash

Photo by National Cancer Institute on Unsplash

Why is it important?

The vast majority of cancer-related death is linked to metastatic dissemination, whereby cancer cells move away from the main tumour and spread throughout the body. To improve anti-cancer treatments, it is therefore important to understand how cancer cell migrate, in order to identify novel drug targets to stop cell migration and invasion.

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