Narciclasine targets STAT3 via distinct mechanisms in tamoxifen-resistant breast cancer cells.

ABSTRACT: STAT3 is constitutively activated in multiple malignant tumors. Compared with regular estrogen receptor (ER)-positive breast cancers, the patients with tamoxifen-resistant breast cancers often exhibit higher levels of STAT3 phosphorylation. Narciclasine (Nar) possesses strong inhibiting effects against a variety of cancer cells; however, the underlying antitumor target(s)/mechanism(s) remains barely understood. In this study, we successfully identified the STAT3 was the direct target of Nar through the combination strategies of connectivity map and drug affinity responsive target stability. In MCF7 cells, Nar could suppress phosphorylation, activation, dimerization, and nuclear translocation of STAT3 by directly binding with the STAT3 SH2 domain. In addition, Nar could specifically degrade

SUBMITTER: Lv C 

PROVIDER: S-EPMC8783118 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature