Abstract 4358: Targeting connexin 43 with α-connexin carboxyl-terminal (ACT1) peptide in breast cancer

Abstract

Expression and functional studies have identified connexins (Cxs), a family of gap junction proteins, as potential tumor suppressors. Studies suggest that connexin 43 (Cx43) has a role in breast cancer cell proliferation, differentiation, and migration. Although pan-gap junction drugs are available, the lack of specificity of these agents increases the opportunity for off target effects. Consequently, a therapeutic agent that specifically modulates Cx43 would be beneficial and has not been tested in breast cancer. In this study, we now test a Cx43 specific agent, called α-connexin carboxyl-terminal (ACT1), in breast cancer. Our studies demonstrate that modulation of Cx43 activity in breast cancer can be effectively achieved with the agent ACT1 to sustain Cx43-mediated gap junctional activity resulting in impaired malignant progression. Furthermore, using ER+ and HER2+ breast cancer cell models, we show that ACT1 treatment enhances the activity of lapatinib and tamoxifen. Citation Format: Christina Grek, Joshua Matthew Rhett, Melissa Abt, Jaclynn Bruce, Gautam Ghatnekar, Elizabeth S. Yeh. Targeting connexin 43 with α-connexin carboxyl-terminal (ACT1) peptide in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4358. doi:10.1158/1538-7445.AM2015-4358