Contact inhibition controls cell survival and proliferation via YAP/TAZ-autophagy axis.
Published version
Repository URI
Repository DOI
Change log
Authors
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.
Description
Keywords
Journal Title
Conference Name
Journal ISSN
2041-1723
Volume Title
Publisher
Publisher DOI
Sponsorship
Cambridge University Hospitals NHS Foundation Trust (CUH) (RG50822)
Wellcome Trust (100140/Z/12/Z)
European Commission (264508)