Uncovering the drivers of primary tumour growth

It is widely known that metastases — cancer cells that have spread from a primary tumour to other parts of the body — are the main cause of cancer-related mortality.  

What triggers metastasis is a subject of intense investigation. Many studies have focused on the epithelial-to-mesenchymal transition (EMT), a process first described in chick embryos in the early 1980s, as a way to explore whether cancer cells might be hijacking this natural developmental process to spread. EMT involves the transformation of cells from an epithelial state, such as those found in the skin and intestine, to a mesenchymal state, such as those in bone, muscle and cartilage. Recently, attention has turned to various proteins that activate EMT, called EMT transcription factors. 

A research team in Spain has now uncovered further evidence pointing to the effects of two EMT transcription factors, named Snail and Serpent, on early tumour progression.  

The researchers observed that EMT transcription factors are often found in benign and in primary tumours — that is, before the onset of metastasis. “This observation motivated us to ask if they may play a role in driving primary tumour growth,” the team says in their paper, published in PLOS Genetics.   

The researchers studied the effects of Snail and Serpent on changes in wing disc size in fruit flies. Wing discs of fly larvae, which later develop into legs, wings and antennae, are commonly used as a model for studying cellular and genetic changes.  

Both Snail and Serpent led to uncontrolled proliferation of wing disc cells. However, Snail was also found to be associated with a decrease in cell size, as well as extensive cell death, which meant that on balance, the overall tissue size did not increase. In contrast, Serpent was associated with an increase in cell size, without cell death, which did lead to an increase in wing disc size.  

Also, when the Serpent-induced tumour-like tissue was transplanted into the abdomen of adult fruit flies, the tissue continued to grow. These results suggest that Serpent induces tissue growth by “triggering cells to proliferate and grow indefinitely,” the researchers say. 

Based on previous findings, they say that Serpent might work by activating several tumour-promoting biological pathways at the same time. These pathways, including ones specifically known as the Yorkie signalling pathway and the Ras pathway, could “act cooperatively both in early stages of primary tumour growth and later in driving invasion and metastasis,” they conclude. 

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