Targeting intracellular B2 receptors using novel cell-penetrating antagonists to arrest growth and induce apoptosis in human triple-negative breast cancer.

ABSTRACT: G protein-coupled receptors (GPCRs) are integral cell-surface proteins having a central role in tumor growth and metastasis. However, several GPCRs retain an atypical intracellular/nuclear location in various types of cancer. The pathological significance of this is currently unknown. Here we extend this observation by showing that the bradykinin B2R (BK-B2R) is nuclearly expressed in the human triple-negative breast cancer (TNBC) cell line MDA-MB-231 and in human clinical specimens of TNBC. We posited that these "nuclearized" receptors could be involved in oncogenic signaling linked to aberrant growth and survival maintenance of TNBC. We used cell-penetrating BK-B2R antagonists, including FR173657 and novel transducible, cell-permeable forms of the peptide B2R antagonist HOE 140 (NG68, NG

SUBMITTER: Dubuc C 

PROVIDER: S-EPMC5839409 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature