One of the key events during cancer metastasis is a process called the epithelial-to-mesenchymal transition (EMT). EMT occurs when genetic changes allow tumor cells to break away and move into different body regions, potentially leading to new tumors in the body. Previous experiments identified specific “stages” of EMT based on the activity of a small number of genes. However, several new studies indicate these stages may not be as distinct as previously thought. Understanding how EMT occurs is a fundamental goal of cancer biology, as it may lead to new cancer treatment options. The Common Fund 4D Nucleome (4DN) program is primed to help by providing scientists with the tools and resources to monitor the changes in gene activity from groups of cells in tumors as well as small changes in individual cells.
4DN program researchers used advanced techniques to look at gene activity over time in single cells. Instead of finding distinct stages linked to EMT, they showed that EMT is actually a continuum of changes within the cell, with multiple genes getting turned on or off at different times. Many of these genes control how our cells make specific proteins that help hold cells in place. By turning these genes off, it may allow tumor cells to break free and move to new regions within the body. The findings also showed why previous experiments indicated EMT occurred in discrete stages. The researchers discovered “checkpoints” within the continuum where different factors regulate how a cell proceeds through the EMT. If any regulatory factors were disrupted, the progress through EMT could stall, making it look as though there were discrete stages to EMT. It was only by looking at single cells over time that the 4DN researchers could explore the continuum of changes and the factors regulating them without being confused by combined results from large groups of cells. These findings begin to shed light on the genetic changes that govern not only EMT in cancer, but diverse biological processes in development and disease. By learning more about the driving forces behind EMT, researchers can start to explore new cancer treatments that prevent or slow metastasis.
Reference
- A pooled single-cell genetic screen identifies regulatory checkpoints in the continuum of the epithelial-to-mesenchymal transition. McFaline-Figueroa JL, Hikk AJ, Qui X, Jackson D, Shendure J, Trapnell C. Nature Genetics, 51, 2019, 1389-1398.
