Priority Research Papers:
Sulforaphane reduces YAP/∆Np63α signaling to reduce cancer stem cell survival and tumor formation
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Matthew L. Fisher1, Nicholas Ciavattone1, Daniel Grun1, Gautam Adhikary1 and Richard L. Eckert1,2,3,4
1 Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA
2 Department of Dermatology, University of Maryland School of Medicine, Baltimore, Maryland, USA
3 Department of Reproductive Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA
4 The Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA
Richard L. Eckert, email:
Keywords: YAP, TAZ, hippo signaling, ∆Np63α;, sulforaphane
Received: July 06, 2017 Accepted: July 31, 2017 Published: August 27, 2017
Epidermal squamous cell carcinoma (SCC) is among the most common cancers. SCC can be treated by surgical excision, but recurrence of therapy-resistant disease is a major problem. We recently showed that YAP1, the Hippo signaling transcription adaptor protein, and ∆Np63α, a key epidermal stem cell survival protein, form a complex to drive epidermal cancer stem cell survival. In the present study, we demonstrate that YAP1 and ∆Np63α are important sulforaphane cancer prevention targets. We show that sulforaphane treatment increases YAP1 phosphorylation and proteolytic degradation. The loss of YAP1 is associated with a reduction in ∆Np63α level and a reduction in ECS cell survival, spheroid formation, invasion and migration. Loss of YAP1 and ∆Np63α is mediated by the proteasome and can be inhibited by lactacystin treatment. YAP1 or ∆Np63α knockdown replicates the responses to sulforaphane, and restoration of YAP1 or ∆Np63α antagonizes sulforaphane action. Sulforaphane suppresses ECS cell tumor formation and this is associated with reduced levels of YAP1 and ∆Np63α. These studies suggest that YAP1 and ∆Np63α may be important sulforaphane cancer preventive targets in epidermal squamous cell carcinoma.
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