Image courtesy of Piril Erler, Ph.D., a co-author of the Nature Cell Biology paper and a postdoctoral fellow in the lab of Wenjun Guo, Ph.D.
Metastasis (the spread of cancer from a primary tumor to other parts of the body) causes 90% of cancer deaths. Wenjun Guo, Ph.D., and colleagues found that mutations in MLL3 (a gene frequently mutated or deleted in breast cancer and other human cancers) allow cancer cells to reversibly switch between epithelial and mesenchymal cell states—transitions crucial for enabling cancer cells to adapt to the changing microenvironments they confront on the way to forming metastases.
In a key experiment, the researchers generated mouse mammary stem-cell organoids (clumps of mostly epithelial cells) in which MLL3 was deleted. As shown here, the MLL3 deletions caused many of the epithelial cells (green) to upregulate the mesenchymal marker vimentin (red), indicating the cells’ partial transition to the mesenchymal state. When transitional cells were injected into the tail veins of mice, they readily seeded in the lungs and formed metastases. The researchers also found that BET (bromodomain and extraterminal) protein inhibitors target MLL3-mutant cells in various types of cancer. The findings were published in January 2023 in Nature Cell Biology. Dr. Guo is an associate professor of cell biology at Einstein.
