Development of CAPER peptides for the treatment of triple negative breast cancer. Issue 4 (16th February 2020)

• Record Type: Journal Article
• Authors: Chilewski, Shannon D.; Bhosale, Devyani; Dees, Sundee; Hutchinson, Isaac; Trimble, Rachel; Pontiggia, Laura; Mercier, Isabelle; Jasmin, Jean-Francois
• Is Part Of: Cell cycle. Volume 19:Issue 4(2020)
• Page Start: 432
• Page End: 447
• Publication Date: 2020-02-16
• Subjects: Triple negative breast cancer -- CAPER -- peptide therapeutics -- RNA binding protein-39 (Rbm39) -- c-Jun -- hepatocellular carcinoma-1.4 (HCC1.4); Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2020.1711579
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Triple negative breast cancer (TNBC) is a heterogeneous disease, which lacks expression of the estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor 2 receptor (HER2). This subtype of breast cancer has the poorest prognosis with limited therapies currently available, and hence additional options are needed. CAPER is a coactivator of the activator protein-1 (AP-1) (interacting specifically with the c-Jun component) and the ER and is known to be involved in human breast cancer pathogenesis. Recent published data have demonstrated a role for CAPER in TNBC and, as such, disrupting the function of CAPER with c-Jun could be a novel approach to treat TNBC patients. The data presented here shows the development and in vitro testing of CAPER-derived peptides that inhibit the coactivator activity of CAPER with c-Jun. These CAPER peptides result in a decrease in cell number and an increase in apoptosis in two TNBC cell lines, MDA-MB-231 and BT-549, while having no effect on the non-tumorigenic cell line MCF 10A. Additionally, two modes of action were demonstrated which appear to be cell line dependent: 1) a modulation of phosphorylated c-Jun leading to a decrease in Bcl-2 in MDA-MB-231 cells and a decrease in p21 in BT-549 cells and 2) a decrease in DNA repair proteins, leading to impaired DNA repair function in MDA-MB-231 cells. The data presented here supports further development of CAPER-derived peptides for the treatment of TNBC.