TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver Malignancy

Publication date: 31 October 2017
Source:Cell Reports, Volume 21, Issue 5
Author(s): Xiao Zhang, Fenyong Sun, Yongxia Qiao, Weisheng Zheng, Ya Liu, Yan Chen, Qi Wu, Xiangfan Liu, Guoqing Zhu, Yuxin Chen, Yongchun Yu, Qiuhui Pan, Jiayi Wang
Although YAP-dependent transcription is closely associated with liver tumorigenesis, the mechanism by which YAP maintains its function is poorly understood. Here, we show that TFCP2 is required for YAP-dependent transcription and liver malignancy. Mechanistically, YAP function is stimulated by TFCP2 via a WW-PSY interaction. TFCP2 also maintains YAP stability by inhibiting βTrCP. Notably, genomic co-occupancy of YAP and TFCP2 is revealed. TFCP2 acts as a transcription co-factor that stimulates YAP transcription by facilitating YAP binding with YAP binding motif (YBF)-containing transcription factors. Interestingly, TFCP2 also stimulated the YAP-TEAD interaction and TEAD target gene expression. Finally, several genes co-regulated by YAP and TFCP2 that contribute to YAP-dependent tumorigenesis are identified and verified. Thus, we establish a model showing that TFCP2 acts as a YAP co-factor to maintain YAP-dependent transcription in liver cancer cells, suggesting that simultaneous targeting of both YAP and TFCP2 may be an effective therapeutic approach.

Graphical abstract

Teaser

Zhang et al. reveal that TFCP2 acts as a YAP co-factor to stimulate YAP-dependent liver malignancy. YAP binds to TFCP2 via a WW-PSY interaction, which facilitates the binding of YAP to transcription factors that contain the YAP binding motif. These effects lead to the enhanced transcription of downstream co-regulated proto-oncogenes.


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