Source: University of Notre Dame
Summary: While seeking to understand cancer cell death, researchers have discovered that the activation of a specific enzyme may help suppress the spread of tumors.
To stop the spread of cancer, cancer cells must die. Unfortunately, many types of cancer cells seem to use innate mechanisms that block cancer cell death, therefore allowing cancer to metastasize. Researchers from the University of Notre Dame have discovered that the activation of a specific enzyme may help suppress the spread of tumors. They demonstrated that the enzyme RIPK1 (receptor-interacting protein kinase) decreases the number of mitochondria in a cell. This loss of mitochondria leads to oxidative stress that can potentially kill cancer cells, though researchers speculate the cancer cells could find ways to shut down this effect. This was surprising, given RIPK1 was well-known to regulate necrosis, a completely distinct cell death mechanism. The study findings were published in the journal Nature Cell Biology.
During the study, the research team discovered that when the enzyme RIPK1 is activated in a cell, it can cause the number of mitochondria considered the “power plants” of the cell to decrease as the cell consumes its own components for energy, a process called mitophagy. The team focused on metastasis, the process by which cancer cells leave the primary tumor and disseminate to other parts of the body. Cell death, a barrier to metastasis, can be induced when epithelial cells, those lining the surfaces of body cavities, detach from the meshwork of scaffolding-like proteins called the extracellular matrix (ECM). As a tumor progresses, it can become resistant to this type of cell death. Thus, RIPK1-mediated induction of mitophagy may be an efficacious target for therapeutics aimed at eliminating ECM-detached cancer cells.
Lead author, Mark Hawk said, “While our findings are in their infancy, we hope we can take advantage of the liability associated with RIPK1’s function in order to design a strategy aimed at eliminating ECM-detached cancer cells, which would ultimately improve patient survival.”
More Information: Mark A. Hawk et al, “RIPK1-mediated induction of mitophagy compromises the viability of extracellular-matrix-detached cells”, Nature Cell Biology (2018). DOI: 10.1038/s41556-018-0034-2