Contact inhibition controls cell survival and proliferation via YAP/TAZ-autophagy axis

Mariana Pavel, Maurizio Renna, So Jung Park, Fiona M. Menzies, Thomas Ricketts, Jens Füllgrabe, Avraham Ashkenazi, Rebecca A. Frake, Alejandro Carnicer Lombarte, Carla F. Bento, Kristian Franze and David C. Rubinsztein ()
Additional contact information
Mariana Pavel: Cambridge Biomedical Campus
Maurizio Renna: Cambridge Biomedical Campus
So Jung Park: Cambridge Biomedical Campus
Fiona M. Menzies: Cambridge Biomedical Campus
Thomas Ricketts: Cambridge Biomedical Campus
Jens Füllgrabe: Cambridge Biomedical Campus
Avraham Ashkenazi: Cambridge Biomedical Campus
Rebecca A. Frake: Cambridge Biomedical Campus
Alejandro Carnicer Lombarte: University of Cambridge
Carla F. Bento: Cambridge Biomedical Campus
Kristian Franze: University of Cambridge
David C. Rubinsztein: Cambridge Biomedical Campus

Nature Communications, 2018, vol. 9, issue 1, 1-18

Abstract: Abstract Contact inhibition enables noncancerous cells to cease proliferation and growth when they contact each other. This characteristic is lost when cells undergo malignant transformation, leading to uncontrolled proliferation and solid tumor formation. Here we report that autophagy is compromised in contact-inhibited cells in 2D or 3D-soft extracellular matrix cultures. In such cells, YAP/TAZ fail to co-transcriptionally regulate the expression of myosin-II genes, resulting in the loss of F-actin stress fibers, which impairs autophagosome formation. The decreased proliferation resulting from contact inhibition is partly autophagy-dependent, as is their increased sensitivity to hypoxia and glucose starvation. These findings define how mechanically repressed YAP/TAZ activity impacts autophagy to contribute to core phenotypes resulting from high cell confluence that are lost in various cancers.

Date: 2018
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DOI: 10.1038/s41467-018-05388-x

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