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YAP‐TEAD signaling promotes basal cell carcinoma development via a c‐JUN/AP1 axis
Author(s) -
Maglic Dejan,
Schlegelmilch Karin,
Dost Antonella FM,
Panero Riccardo,
Dill Michael T,
Calogero Raffaele A,
Camargo Fernando D
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798642
Subject(s) - biology , ap 1 transcription factor , signal transduction , cancer research , microbiology and biotechnology , genetics , transcription factor , gene
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 .