Sulforaphane reduces YAP/∆Np63α signaling to reduce cancer stem cell survival and tumor formation

// Matthew L. Fisher 1 , Nicholas Ciavattone 1 , Daniel Grun 1 , Gautam Adhikary 1 and Richard L. Eckert 1,2,3,4 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 Correspondence to: Richard L. Eckert, email: // Keywords : YAP, TAZ, hippo signaling, ∆Np63α;, sulforaphane Received : July 06, 2017 Accepted : July 31, 2017 Published : August 27, 2017 Abstract 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.