Journal
NATURE COMMUNICATIONS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms5629
Keywords
-
Categories
Funding
- National Basic Research Program of China (973 Program) [2012CB945001, 2012CB910800, 2010CB912102]
- National Natural Science Foundation of China [81101583, 81372509, 31370747, 81325015]
- Science and Technology Commission of Shanghai Municipality [12JC1409800 JHB]
- 'Cross and Cooperation in Science and Technology Innovation Team' programme, Shanghai Institutes for Biological Sciences [2012KIP502]
- China Postdoctoral Science Foundation [2011M500826]
- Sanofi-Aventis Shanghai Institutes for Biological Sciences (SA-SIBS) scholarship programme
- K.C. Wong education foundation scholarship
Ask authors/readers for more resources
Whether the Hippo pathway contributes to cell lineage transition under pathological conditions, especially tumorigenesis, remains largely unknown. Here we show that YAP, the major effector of the Hippo pathway, displays a distinct activation pattern in lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC); YAP is initially activated by LKB1 loss in lung ADC, which upregulates ZEB2 expression and represses DNp63 transcription in a default manner. During transdifferentiation, YAP is inactivated, which in turn relieves ZEB2-mediated default repression of DNp63 and triggers squamous differentiation reprogramming. Disruption of the YAP barrier for phenotypic transition significantly accelerates squamous transdifferentiation, whereas constitutive YAP activation conversely inhibits this transition. More importantly, ectopic DNp63 expression rescues the inhibitory effect of YAP on squamous transdifferentiation. These findings have established YAP as an essential barrier for lung cancer cell fate conversion and provided a mechanism for regulating cancer plasticity, which might hold important implication for YAP-targeted therapies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available