Deregulated TGF-β signalling in cancer


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Caroline Hill1
1The Francis Crick Institute

Abstract

Deregulated TGF-β signalling has long been known to play a key role in many different types of cancer. We are studying the mechanism of TGF-β signalling to understand better how the pathway is deregulated in cancer, and to pinpoint exactly what roles TGF-β signalling plays in tumour growth and spread. Two recent key findings from my lab have made us re-evaluate the role of TGF-β signalling in cancer. Firstly, we discovered that cells treated acutely with TGF-β become refractory to further stimulation. This means that cells experiencing prolonged chronic TGF-β signalling counterintuitively exhibit very low signalling activity. This suggested that in cancer, where tumours frequently exhibit high levels of TGF-β signalling, the TGF-β pathway might be rewired. I will discuss the results from a loss-of-function screen designed to identify mechanisms that alter the dynamics of TGF-β signalling. Secondly, we have shown that TGF-β not only signals through SMAD2/3, but also through SMAD1/5, the receptor-regulated SMADs that are traditionally thought to be activated by BMP signalling. Importantly, we have shown that both pathways are essential for TGF-β-induced EMT. I will discuss our recent insights into the role of SMAD1/5 signalling in cancer.