EDITOR'S CHOICE IN DISEASE AND MEDICINE
COURTESY OF HUA GAO AND FILIPPO GIANCOTTI
H. Gao et al., “The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites.” Cell, 150:764-79, 2012.
Cancer cells often move around early in tumor development, but can remain dormant for years. Hua Gao and colleagues at the Sloan-Kettering Institute for Cancer Research discovered that dormant breast cancer cells that have migrated to the lung could be roused when they start to express a protein called Coco, which is switched on by an unknown signal from lung tissue and fires up the cell’s transition to an active cancer stem cell.
The alarm clock
To identify genes involved in metastasis, Gao and colleagues screened fragments of DNA from highly metastatic cancer cells by inserting them into poorly metastatic cancer cells, and injecting those cells into the breast tissue of mice. Some cells that successfully metastasized to the lung carried a gene encoding the protein Coco, which had not been previously linked to metastasis.
Only those Coco-gene-carrying cancer cells that ended up in the lung became proliferative, or fully metastatic. The reason, the researchers discovered, is that Coco blocks secreted regulators, called bone morphogenetic proteins (BMP)—expressed at high levels in the lung—which prevent cancer cells from transitioning to a proliferative stem-cell state. Coco’s wake-up call is limited to the lung because other organs may have sentinel regulators in addition to BMP that block stem-cell activation. In the lung, Coco’s activation can single-handedly switch the cancer cell from a dormant state to an active stem cell.
The fresh take
Though the authors don’t know what switches Coco on in the lung, before this study “there was no connection between Coco and cancer, let alone metastasis,” says Filippo Giancotti, a cell biologist at Sloan-Kettering and senior researcher on the study.