Cells on the (Invasion) Front Lines
Long thought to be a key component of the metastatic process, researchers are now questioning long-held beliefs of the role of epithelial-to-mesenchymal transition
Michael Schubert |
The diagnosis and treatment of cancer has moved ahead by leaps and bounds – except when it comes to metastatic disease. Cancer that has spread beyond its origins remains the leading cause of death from the disease, according to the World Health Organization, and although it’s a major focus of research, we know little more about its mechanisms today than we did a decade or more ago. This is especially true when it comes to the epithelial-to-mesenchymal transition (EMT), a key component of the metastatic process… or is it?
The debate over EMT’s significance in cancer spreading is a fierce and ongoing one, largely due to the difficulties inherent in observing and understanding it. Why are researchers so convinced of EMT’s role in metastasis? It’s well known that mesenchymal cells are more capable of escaping the primary tumor, and of taking up residence in distant sites. But the evidence against EMT-driven metastasis is mounting, too – most cells in metastatic lesions exhibit epithelial, not mesenchymal, characteristics. Some scientists refer to the reverse process, mesenchymal-to-epithelial transition (MET) to explain this behavior, but others aren’t so sure. At the root of the confusion is a lack of evidence. Until the entire metastatic process – local invasion, intravasation, circulation, arrest and extravasation, proliferation, and angiogenesis – is observed in mesenchymal cells, the role of EMT in metastasis remains an open question.
Despite the debate, many researchers simply take EMT’s role in metastasis as read. Searching the PubMed database for “EMT and metastasis” brings up 3,675 publications, and even Wikipedia – the first port of call for most non-experts without access to peer-reviewed articles – boldly states, “EMT and MET form the initiation and completion of the invasion-metastasis cascade.” There’s little indication of doubt, and yet, recent studies are threatening to completely overhaul the research community’s view of EMT and metastasis. Exactly how do these two aspects of cancer biology interact? The quest to understand is more intense than ever, thanks to groundbreaking new data from research groups whose conclusions go against the grain.