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

ABSTRACT: Coactivator-associated arginine methyltransferase 1 (CARM1/PRMT4) is well-known for its essential physiological functions and its pivotal role in the development and progression of various cancers. 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. In conclusion, we present a novel peptide inhibitor of CARM1, which provides valuable insights and holds substantial therapeutic potential for the development of CARM1-targeted treatments in breast cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE285651 | GEO | 2026/03/19

REPOSITORIES: GEO

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A CARM1 inhibitor potently suppresses breast cancer both in vitro and in vivo

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