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EMBO Rep. 2018 Jul;19(7). pii: e45809. doi: 10.15252/embr.201845809. Epub 2018 Jun 6.

YAP and TAZ are essential for basal and squamous cell carcinoma initiation.

Author information

1
Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles, Brussels, Belgium.
2
Department of Pathology, Erasme University Hospital, University Libre de Bruxelles, Brussels, Belgium.
3
Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles, Brussels, Belgium cedric.blanpain@ulb.ac.be.
4
WELBIO, Université Libre de Bruxelles, Brussels, Belgium.

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.

KEYWORDS:

TAZ; YAP; basal cell carcinoma; cancer; squamous cell carcinoma

PMID:
29875149
PMCID:
PMC6030692
[Available on 2019-07-01]
DOI:
10.15252/embr.201845809

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