The interplay between IGF-1R signaling and Hippo-YAP in breast cancer stem cells

Cell Communication and Signaling

卷:21

Brief Report

Jyh-Cherng Yu¹  Ruey-Jen Lin²  Yu-Tzu Chan²  Tsai-Hsien Hung²  Ya-Hui Wang²  John Yu³  Alice L. Yu⁴  Yenlin Huang⁵ 

[1] Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan;

[2] Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan;

[3] Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan;Chang Gung University, Taoyuan, Taiwan;

[4] Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan;Chang Gung University, Taoyuan, Taiwan;Department of Pediatrics, University of California in San Diego, San Diego, CA, USA;Genomics Research Center, Academia Sinica, Taipei, Taiwan;

[5] Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan;Department of Anatomic Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan;School of Medicine, National Tsing-Hua University, Hsinchu, Taiwan;

关键词: Hippo;    YAP;    IGF-1;    IGF-1R;    Breast cancer stem cells;   

DOI  :  10.1186/s12964-023-01088-2

 received in 2023-01-06, accepted in 2023-02-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundBoth IGF-1R/PI3K/AKT/mTOR and Hippo pathways are crucial for breast cancer stem cells (BCSCs). However, their interplay remains unclear.MethodsFour triple negative breast cancer cell lines derived from CSC of two patient-derived xenografts (PDXs), AS-B145, AS-B145-1R, AS-B244, and AS-B244-1R, were used to elucidate the role of YAP in BCSCs. YAP silenced BCSCs were analyzed by cell proliferation, aldehyde dehydrogenase (ALDH) activity, mammosphere formation, and tumorigenesis. The effects of modulating IGF-1R and IGF-1 on YAP expression and localization were evaluated. The clinical correlation of YAP and IGF-1R signaling with the overall survival (OS) of 7830 breast cancer patients was analyzed by KM plotter.ResultsKnockdown of YAP abates the viability and stemness of BCSCs in vitro and tumorigenicity in vivo. Depletion of IGF-1R by shRNA or specific inhibitor decreases YAP expression. In contrast, IGF-1 addition upregulates YAP and enhances its nuclear localization. YAP overexpression increased the mRNA level of IGF-1, but not IGF-1R. Data mining of clinical breast cancer specimens revealed that basal-like breast cancer patients with higher level of IGF-1 and YAP exhibit significantly shorter OS.ConclusionsYAP contributes to stemness features of breast cancer in vitro and in vivo. The expression and localization of YAP was regulated by IGF-1R and YAP expression in turns upregulates IGF-1, but not IGF-1R. Clinically, higher level of YAP and IGF-1 significantly correlated with shorter OS in basal-like breast cancer. Taken together, these findings suggest the clinical relevance of interplay between YAP and IGF-1/IGF-1R pathway in sustaining the properties of BCSCs.DsuDGZeKddKHpMfgDukzC_Video Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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