CK2-mediated phosphorylation of SF3B3 enhances its deubiquitination and stability to promote aberrant alternative splicing and ESCC progression

Targeted inhibition of CARM1 activity has emerged as a promising strategy for cancer treatment. Herein, we report a peptide inhibitor of CARM1, Pi-CARM1. which demonstrates high selectivity for CARM1.

The cell-permeable form of Pi-CARM1, Pi-CARM1-TAT, effectively suppresses breast cancer cell proliferation in vitro and significantly reduces tumor growth in mouse models of breast cancer. Mechanistically, Pi-CARM1-TAT recapitulates the impact of CARM1 on the expression of oncogenic estrogen/ERα-target genes, as well as type I interferon (IFN) and IFN-induced genes (ISGs) in breast cancer cells. Notably, the combination of Pi-CARM1-TAT with endocrine therapy drugs or etoposide shows synergistic effects in inhibiting breast tumorigenesis.