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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Carcinoma, Basal Cell / genetics*
  • Carcinoma, Basal Cell / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle Proteins
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Nucleus / genetics
  • Cell Proliferation / genetics
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Mice
  • Mice, Knockout
  • Phosphoproteins / genetics*
  • Signal Transduction / genetics
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Transcription Factors / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Transcription Factors
  • WWTR1 protein, human
  • Wwtr1 protein, mouse
  • YAP1 (Yes-associated) protein, human
  • Yap protein, mouse