A recent article by Dr Mariana Pavel from Professor David Rubinsztein’s lab, Department of Medical Genetics, Cambridge Institute for Medical Research, identifies that contact inhibition, the process that normally limits cell proliferation and growth when cells contact each other, suppresses autophagy. Contact inhibition is lost in cancerous cells and this leads to tumour formation. Although it is known that cells normally respond to changes in their mechanical environment as they reach high density through activation of Hippo signalling and downstream YAP/TAZ co-transcriptional regulators, much remains to be learnt about the consequences of this.
Published in Nature Communications, the Rubinsztein lab now find that inhibition of cellular recycling through autophagy is a vital component of this process. They show that the mechanical inhibition of YAP/TAZ-mediated transcription, initiated upon contact inhibition, in turn disrupts autophagosome formation and that this is important for subsequent reduced cell proliferation. They also speculate that the increased autophagy in particular cancers may also provide metastatic advantage to tumour cells.