Mechanisms behind aggressive cancer metastases uncovered
Breast cancer spreading to other organs usually heralds a poorer prognosis. Researchers at the University and University Hospital of Basel have discovered a process that helps breast cancer cells implant themselves in certain places in the body. The results suggest a way of preventing secondary tumors.
06 June 2023 | Angelika Jacobs
For eight years, a team led by Professor Mohamed Bentires-Alj worked to establish the role of a cellular enzyme in breast cancer metastasis. The three lead authors Joana Pinto Couto, Milica Vulin, Charly Jehanno and collaborators discovered a mechanism that appears to support metastasis in a range of aggressive cancers. The team has reported their findings in the Embo Journal.
A cell can be pictured like a social network: in theory, every person is connected to every other person in the world through surprisingly few degrees of separation. Cell factors in molecular networks are connected to each other in an analogous way. If one stops functioning correctly, the system is thrown out of balance. The result is a cascade of effects that can have wide-ranging and unexpected consequences on more distant parts of the network. Deciphering these cascades can contribute to our understanding of how a minordefect in a cell’s system can lead to diseases like cancer. These insights offer ideas for new treatments.
Bentires-Alj’s research team at the Department of Biomedicine, University of Basel and University Hospital Basel, elucidated one of these cascades. It begins with a metabolic enzyme called nicotinamide N-methyltransferase, or NNMT for short. And it ends with the substance that fills the space between the body’s cells and holds them together: collagen. Collagen is actually a good thing. But in the case of metastatic cancer, it betrays the body and helps cancer cells embed themselves in new tissues.
Wandering cancer cells with their own collagen
“Triple negative” breast cancer, which affects roughly 15 percent of all breast cancer patients, is particularly aggressive because it often spreads throughout the body and forms lung and brain metastases. These breast cancer cells produce unusually high amounts of NNMT. As the researchers learned through experiments on animals, overproduction of NNMT is key to the metastasis.
Joana Pinto Couto, Milica Vulin, Charly Jehanno et al.
Nicotinamide N-methyltransferase sustains a core epigenetic program that promotes metastatic colonization in breast cancer
Embo Journal (2023), doi: 10.15252/embj.2022112559