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

First Author  Debaugnies M Year  2018
Journal  EMBO Rep Volume  19
Issue  7 PubMed ID  29875149
Mgi Jnum  J:264822 Mgi Id  MGI:6188458
Doi  10.15252/embr.201845809 Citation  Debaugnies M, et al. (2018) YAP and TAZ are essential for basal and squamous cell carcinoma initiation. EMBO Rep 19(7)
abstractText  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.
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