YAP promotes chromosomal instability by transcriptionally activating AJUBA through its super enhancer in breast cancer

Huang, Q.; Zhang, R.; Meng, W.; Dong, H.; Qi, Z.; Chen, Z.; Liu, L.; Shen, J.; Xie, D.

doi:10.1101/2024.02.19.579918

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bioRxiv · 10.1101/2024.02.19.579918

YAP promotes chromosomal instability by transcriptionally activating AJUBA through its super enhancer in breast cancer

Huang, Q.·Zhang, R.·Meng, W.·Dong, H.·Qi, Z.·Chen, Z.·Liu, L.·Shen, J.·Xie, D.

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Abstract

Chromosomal instability (CIN) has been proven to be a fundamental property of cancer and a key underlying mechanism of tumorigenesis and progression. Still, relatively few studies have revealed the mechanism of this process. In this research, we identified the core Hippo component, YAP, played a crucial role in CIN formation in breast cancer. Using public ChIP-seq data and bioinformatic analysis, we found YAP could transcriptionally induce spindle assembly checkpoint, AJUBA, via TEAD, then activate AJUBA-AURKA signaling. Abolish AJUBA-AURKA axis could reverse YAP-induced CIN formation and aberrant mitosis. Mechanically, YAP/TEAD complex could accumulate to the super enhancer region of AJUBA, thus significantly induced its expression, and subsequently promoted AURKA auto-phosphorylating. These findings revealed a novel cross-talk between Hippo and AJUBA-AURKA signaling, and provided a new insight in CIN formation in breast cancer.

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Huang, Q., Zhang, R., Meng, W., Dong, H., Qi, Z., Chen, Z., Liu, L., Shen, J., Xie, D.. 2024-02-21. YAP promotes chromosomal instability by transcriptionally activating AJUBA through its super enhancer in breast cancer. https://doi.org/10.1101/2024.02.19.579918

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