LEF1 enhances β-catenin transactivation through IDR-dependent liquid–liquid phase separation

ABSTRACT: This research elucidates the correlation between liquid–liquid phase separation (LLPS) of LEF1 with β-catenin and their transcriptional activation function, offering a novel therapeutic approach for the treatment of colorectal cancer through LLPS. 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

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PROVIDER: S-EPMC10474303 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature