A PROTAC peptide induces durable β-catenin degradation and suppresses Wnt-dependent intestinal cancer.

ABSTRACT: Aberrant activation of Wnt/β-catenin signaling has been associated with the onset and progression of many types of tumors and thus β-catenin represents one attractive intracellular target for cancer therapy. Based on the Axin-derived peptide that binds to β-catenin, two stapled peptides SAHPA1 and xStAx were reported to enhance or impair Wnt/β-catenin signaling, respectively. In this study, we designed PROTACs (proteolysis targeting chimeras) by coupling SAHPA1 or xStAx with the VHL ligand to achieve efficient β-catenin degradation. The obtained xStAx-VHLL sustained β-catenin degradation and manifested strong inhibition of Wnt signaling in cancer cells and in APC^-/- organoids. Furthermore, xStAx-VHLL could effectively restrain tumor formation in BALB/C nude mice, a

SUBMITTER: Liao H 

PROVIDER: S-EPMC7280531 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature