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

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Item Type:	Article
Title:	YAP and β-catenin cooperate to drive oncogenesis in basal breast cancer
Creators Name:	Quinn, H.M., Vogel, R., Popp, O., Mertins, P., Lan, L., Messerschmidt, C., Landshammer, A., Lisek, K., Château-Joubert, S., Marangoni, E., Koren, E., 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
Volume:	81
Number:	8
Page Range:	2116-2127
Date:	April 2021
Official Publication:	https://doi.org/10.1158/0008-5472.CAN-20-2801
PubMed:	View item in PubMed

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