Blockade of Nuclear β-Catenin Signaling via Direct Targeting of RanBP3 with NU2058 Induces Cell Senescence to Suppress Colorectal Tumorigenesis.

ABSTRACT: Colorectal cancer (CRC) is one of the most common malignant tumors in the world, with high prevalence and low 5-year survival. Most of the CRC patients show excessive activation of the Wnt/β-catenin pathway which is a vital target for CRC treatment. Based on multiple CRC cell lines with different nuclear expression of β-catenin, NU2058 is identified from a small molecule library consisting of 280 bioactive compounds and found to selectively inhibit the proliferation of CRC cells with nuclear β-catenin activation in vitro and in vivo. The translational significance of NU2058 alone or in combination with chemotherapeutic drugs oxaliplatin and irinotecan (SN38) in CRC is demonstrated in orthotopic tumor model and patient-derived xenograft models. By integrating limited proteolysis-small molec

SUBMITTER: Zheng CC 

PROVIDER: S-EPMC9731691 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature