PT - JOURNAL ARTICLE AU - Zhao, Bing AU - Li, Zhuoxin AU - Yu, Shaoqing AU - Li, Tingting AU - Wang, Wen AU - Liu, Ran AU - Zhang, Biyu AU - Fang, Xiya AU - Shen, Yezhuang AU - Han, Qiuying AU - Xu, Xin AU - Wang, Kai AU - Gong, Weili AU - Li, Tao AU - Li, Ailing AU - Zhou, Tao AU - Li, Weihua AU - Li, Teng TI - LEF1 enhances β-catenin transactivation through IDR-dependent liquid–liquid phase separation AID - 10.26508/lsa.202302118 DP - 2023 Nov 01 TA - Life Science Alliance PG - e202302118 VI - 6 IP - 11 4099 - http://www.life-science-alliance.org/content/6/11/e202302118.short 4100 - http://www.life-science-alliance.org/content/6/11/e202302118.full SO - Life Sci. Alliance2023 Nov 01; 6 AB - Wnt/β-catenin signaling plays a crucial role in cancer development, primarily activated by β-catenin forming a transcription complex with LEF/TCF in the nucleus and initiating the transcription of Wnt target genes. Here, we report that LEF1, a member of the LEF/TCF family, can form intrinsically disordered region (IDR)-dependent condensates with β-catenin both in vivo and in vitro, which is required for β-catenin-dependent transcription. Notably, LEF1 with disrupted IDR lost its promoting activity on tumor proliferation and metastasis, which can be restored by substituting with FUS IDR. Our findings provide new insight into the essential role of liquid–liquid phase separation in Wnt/β-catenin signaling and present a potential new target for cancer therapy.