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EMBO J. 2018 Sep 3;37(17). pii: e98642. doi: 10.15252/embj.201798642. Epub 2018 Jul 23.

YAP-TEAD signaling promotes basal cell carcinoma development via a c-JUN/AP1 axis.

Author information

1
Stem Cell Program, Boston Children's Hospital, Boston, MA, USA.
2
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
3
The Francis Crick Institute, Tumour Cell Biology, London, UK.
4
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy.
5
Stem Cell Program, Boston Children's Hospital, Boston, MA, USA fernando.camargo@childrens.harvard.edu.

Abstract

The mammalian Hippo signaling pathway, through its effectors YAP and TAZ, coerces epithelial progenitor cell expansion for appropriate tissue development or regeneration upon damage. Its ability to drive rapid tissue growth explains why many oncogenic events frequently exploit this pathway to promote cancer phenotypes. Indeed, several tumor types including basal cell carcinoma (BCC) show genetic aberrations in the Hippo (or YAP/TAZ) regulators. Here, we uncover that while YAP is dispensable for homeostatic epidermal regeneration, it is required for BCC development. Our clonal analyses further demonstrate that the few emerging Yap-null dysplasia have lower fitness and thus are diminished as they progress to invasive BCC Mechanistically, YAP depletion in BCC tumors leads to effective impairment of the JNK-JUN signaling, a well-established tumor-driving cascade. Importantly, in this context, YAP does not influence canonical Wnt or Hedgehog signaling. Overall, we reveal Hippo signaling as an independent promoter of BCC pathogenesis and thereby a viable target for drug-resistant BCC.

KEYWORDS:

YAP ; AP1; Hippo signaling; Jun; basal cell carcinoma

PMID:
30037824
PMCID:
PMC6120663
[Available on 2019-09-03]
DOI:
10.15252/embj.201798642

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