Abstract 4447: EZH2 contributes to breast cancer metastasis

While the 5-year relative survival rate of localized stage breast cancer is 99%, once the cancer spreads to distant lymph nodes and organs the survival rate falls to 25%. In order to develop strategies to combat metastasis, we have been studying epigenetic factors that contribute to the aggressive nature of breast cancer. We have focused on enhancer of zeste homolog 2 (EZH2), a histone methyl transferase, because breast cancer patients expressing increased EZH2 exhibit highest metastatic recurrence. We have found through in vivo studies that blocking EZH2 activity not only prevents metastasis formation, but also targets established metastases. Genome wide ChIP-seq analysis revealed that EZH2 may impact breast cancer metastasis through regulating the expression of EMT marker, E-cadherin, and stem cell markers, GATA3 and DKK2. Mammosphere assays from tumors treated with pharmacological blockade of EZH2 and limiting dilution analysis validates that EZH2 inhibition impacts the tumor-initiating cell population. Our data suggests that inhibition of EZH2 activity may have anti-metastatic therapeutic potential and may complement current standards of breast cancer therapy. Citation Format: Shira Yomtoubian, Seongho Ryu, Sharrell Lee, Lauren Havel, Dingcheng Gao, Vivek Mittal. EZH2 contributes to breast cancer metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4447.