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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.

2024-02-21 cancer biology
10.1101/2024.02.19.579918 bioRxiv
Show 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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