Metastasis causes approximately 90% of all cancer-related deaths. In August, a team of researchers led by Ludwig Chicago Co-director Ralph Weichselbaum and Ronald Rock of the University of Chicago described in the Proceedings of the National Academy of Sciences a potentially new way to hamper the process. They reported that a compound, 4-hydroxyacetophenone (4-HAP), compromises the ability of cancer cells to change shape and migrate by activating a protein in the cancer cell called nonmuscle myosin-2C (NM2C). This protein helps control the stiffness of cells and organizes components of the cytoskeleton known as actin filaments that play a central role in cell motility. On the basis of evidence from some elegant microscopy, Ronald, Ralph and colleagues hypothesized that NM2C’s abnormal activation freezes it on certain types of actin filaments, gumming up the machinery of cellular migration. When colon cancer cells were injected into the spleen in a mouse model for liver metastasis, dosing the animals with 4-HAP significantly reduced the burden of tumors compared to untreated counterparts. Although 4-HAP is not likely to work as a drug, the researchers now have a druggable target—NM2C—against metastasis and hope to evaluate the combination of NM2C activation in animals with radiotherapy or chemotherapy.
This article appeared in the December 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).