Dataset Information

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

ABSTRACT:

Background

Both IGF-1R/PI3K/AKT/mTOR and Hippo pathways are crucial for breast cancer stem cells (BCSCs). However, their interplay remains unclear.

Methods

Four 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.

Results

Knockdown 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.

Conclusions

YAP 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. Video Abstract.

SUBMITTER: Chan YT

PROVIDER: S-EPMC10120239 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Chan Yu-Tzu YT Lin Ruey-Jen RJ Wang Ya-Hui YH Hung Tsai-Hsien TH Huang Yenlin Y Yu John J Yu Jyh-Cherng JC Yu Alice L AL

Cell communication and signaling : CCS 20230420 1

<h4>Background</h4>Both IGF-1R/PI3K/AKT/mTOR and Hippo pathways are crucial for breast cancer stem cells (BCSCs). However, their interplay remains unclear.<h4>Methods</h4>Four 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 tumori ...[more]

PMID: 37081542

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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