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YAP and β-catenin cooperate to drive oncogenesis in basal breast cancer

Item Type:Article
Title:YAP and β-catenin cooperate to drive oncogenesis in basal breast cancer
Creators Name:Quinn, H.M. and Vogel, R. and Popp, O. and Mertins, P. and Lan, L. and Messerschmidt, C. and Landshammer, A. and Lisek, K. and Château-Joubert, S. and Marangoni, E. and Koren, E. and Fuchs, Y. and Birchmeier, W.
Abstract:Targeting cancer stem cells (CSC) can serve as an effective approach toward limiting resistance to therapies. While basal-like (triple-negative) breast cancers encompass cells with CSC features, rational therapies remain poorly established. We show here that the receptor tyrosine kinase Met promotes YAP activity in basal-like breast cancer and find enhanced YAP activity within the CSC population. Interfering with YAP activity delayed basal-like cancer formation, prevented luminal to basal trans-differentiation, and reduced CSC. YAP knockout mammary glands revealed a decrease in β-catenin target genes, suggesting that YAP is required for nuclear β-catenin activity. Mechanistically, nuclear YAP interacted with β-catenin and TEAD4 at gene regulatory elements. Proteomic patient data revealed an upregulation of the YAP signature in basal-like breast cancers. Our findings demonstrate that in basal-like breast cancers, β-catenin activity is dependent on YAP signalling and controls the CSC program. These findings suggest that targeting the YAP/TEAD4/β-catenin complex offers a potential therapeutic strategy for eradicating CSCs in basal-like breast cancers.
Keywords:Breast Cancer, Cancer Stem Cells, YAP, Wnt Signalling, Animals, Mice
Source:Cancer Research
ISSN:0008-5472
Publisher:American Association for Cancer Research
Date:11 February 2021
Official Publication:https://doi.org/10.1158/0008-5472.CAN-20-2801
PubMed:View item in PubMed

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