YAP and TAZ are essential for basal and squamous cell carcinoma initiation. (6th June 2018)

• Record Type: Journal Article
• Authors: Debaugnies, Maud; Sánchez‐Danés, Adriana; Rorive, Sandrine; Raphaël, Maylis; Liagre, Mélanie; Parent, Marie‐Astrid; Brisebarre, Audrey; Salmon, Isabelle; Blanpain, Cédric
• Is Part Of: EMBO reports. Volume 19:Number 7(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-06-06
• Subjects: basal cell carcinoma -- cancer -- squamous cell carcinoma -- YAP -- TAZ; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201845809
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: YAP and TAZ are key downstream regulators of the Hippo pathway, regulating cell proliferation and differentiation. YAP and TAZ activation has been reported in different cancer types. However, it remains unclear whether they are required for the initiation of major skin malignancies like basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Here, we analyze the expression of YAP and TAZ in these skin cancers and evaluate cancer initiation in knockout mouse models. We show that YAP and TAZ are nuclear and highly expressed in different BCC types in both human and mice. Further, we find that cells with nuclear YAP and TAZ localize to the invasive front in well‐differentiated SCC, whereas nuclear YAP is homogeneously expressed in spindle cell carcinoma undergoing EMT. We also show that mouse BCC and SCC are enriched for YAP gene signatures. Finally, we find that the conditional deletion of YAP and TAZ in mouse models of BCC and SCC prevents tumor formation. Thus, YAP and TAZ are key determinants of skin cancer initiation, suggesting that targeting the YAP and TAZ signaling pathway might be beneficial for the treatment of skin cancers. Synopsis: The Hippo pathway transcription factors YAP and TAZ are expressed and active in basal and squamous cell carcinoma in mice and humans. Conditional deletion of YAP and TAZ in mouse models prevents skin cancer initiation. YAP and TAZ are expressed in mouse and human basal and squamous cell carcinoma. YAP and TAZ are mainly nuclear in basal and squamous cell carcinoma. Basal and squamous cell carcinomas express YAP gene signatures. Conditional deletion of YAP and TAZ prevents skin cancer initiation in mice. Abstract : The Hippo pathway transcription factors YAP and TAZ are expressed and active in basal and squamous cell carcinoma in mice and humans. Conditional deletion of YAP and TAZ in mouse models prevents skin cancer initiation.