Abstract P2-05-23: TWIST1 silences FOXA1 transcription to promote breast cancer progression

Abstract

Abstract TWIST1 promotes epithelial-mesenchymal transition (EMT), invasion and metastasis of breast cancer cells, but the underlying mechanism is still not well understood. We generated mammary gland tumor specific Twist1 knock out mouse model and found that TWIST1 does not affect PyMT-induced mammary tumor initiation and growth but promotes tumor lung metastasis. We identified FOXA1 as a novel direct target of TWIST1 in both mouse and human breast cancer. We further found that TWIST1 inhibits FOXA1 expression through direct binding to its proximal promoter region and recruiting Mi2/nucleosome remodeling and deacetylase (Mi2/NuRD) transcriptional repressor complex. Moreover, TWIST1 also diminished transcriptional activator AP1 binding to FOXA1 promoter. TWIST1 mediated FOXA1 down-regulation is essential for promoting breast cancer migration, invasion and metastasis. FOXA1 significantly inhibits TWIST1 dependent cell migration and invasion capability of MCF7 cells through inhibiting integrin α5, β1 and MMP9 expression. Importantly, TWIST1high FOXA1low correlates with the poorest prognosis in breast cancer patients. Citation Format: Xu Y, Feng Z, Xu Y, Mo Q, Qin L, Sun T, Wu H, Li Y, Liao L, Xu J. TWIST1 silences FOXA1 transcription to promote breast cancer progression. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-23.