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00085472can202801-sup-249632_2_supp_6883591_qnr73t.png (3.58 MB)

Supplementary Figure 3 from YAP and β-Catenin Cooperate to Drive Oncogenesis in Basal Breast Cancer

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posted on 2023-03-31, 04:45 authored by Hazel M. Quinn, Regina Vogel, Oliver Popp, Philipp Mertins, Linxiang Lan, Clemens Messerschmidt, Alexandro Landshammer, Kamil Lisek, Sophie Château-Joubert, Elisabetta Marangoni, Elle Koren, Yaron Fuchs, Walter Birchmeier

Supplementary figure related to figure 3. Supplementary Fig. 3. Wnt-Met signalling induces YAP-dependent luminal-to-basal transition.

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ARTICLE 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 transdifferentiation, 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 signaling 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. These findings show that YAP cooperates with β-catenin in basal-like breast cancer to regulate CSCs and that targeting this interaction may be a novel CSC therapy for patients with basal-like breast cancer.

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