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

Autor: Mélanie Liagre, Cédric Blanpain, Isabelle Salmon, Audrey Brisebarre, Marie‐Astrid Parent, Maud Debaugnies, Adriana Sánchez-Danés, Maylis Raphaël, Sandrine Rorive
Rok vydání: 2018
Předmět:
0301 basic medicine
Skin Neoplasms
Cell Cycle Proteins
Biology
Biochemistry
Mice
03 medical and health sciences
Cell Line
Tumor
Genetics
medicine
Animals
Humans
Basal cell carcinoma
Molecular Biology
Adaptor Proteins
Signal Transducing
Cell Proliferation
Cell Nucleus
Mice
Knockout
Hippo signaling pathway
integumentary system
Cell growth
Scientific Reports
Intracellular Signaling Peptides and Proteins
Cancer
Cell Differentiation
YAP-Signaling Proteins
Phosphoproteins
medicine.disease
Gene Expression Regulation
Neoplastic
Disease Models
Animal
030104 developmental biology
Carcinoma
Basal Cell
Transcriptional Coactivator with PDZ-Binding Motif Proteins
Knockout mouse
Carcinoma
Squamous Cell
Trans-Activators
Cancer research
Skin cancer
Signal transduction
Spindle cell carcinoma
Signal Transduction
Transcription Factors
Zdroj: EMBO reports. 19
ISSN: 1469-3178
1469-221X
DOI: 10.15252/embr.201845809
Popis: 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.
Databáze: OpenAIRE
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