Abstract P1-05-02: The N-terminus of Twist1 is responsible for interacting with transcriptional repressors to promote EMT and metastasis of breast cancer cells

Twist1, a basic helix-loop-helix transcription factor, plays a key role to mediate epithelial-mesenchymal transition (EMT) and promote breast cancer metastasis. However, knowledge about Twist1 structure-function relationships to cancer-related phenotypes is limited. Therefore, we studied the requirement of Twist1 N-terminus in Twist1-dependent breast cancer metastasis. We showed that the amino-terminus of Twist1 was the dominant negative mutant of Twist1. Overexpression of Twist1 N-terminus exhibited different cell morphology and motility in vitro. Inoculation of Twist1 N-terminus overexpression cells into SCID mice showed delayed tumor formation and reduced lung metastasis. Furthermore, Twist1 N-terminus overexpression induced expression change of EMT markers, including E-cadherin, β-catenin, vimentin and Twist1 both in vivo and in vitro. Co-immunoprecipitation and mass spectrometry revealed that Twist1 N-terminus interacted with several members of the Mi2/nucleosome remodeling and deacetylase (Mi2/NuRD) complex, HDAC2, 3 and 7, MTA1 and 2, RbAp46/48, and many corepressors including NCoR1 and 2, which released them from the proximal region of E-cadherin promoter for transcriptional activation. These data suggest that Twist1 N-terminus is required for Twist1-mediated transcriptional programs and breast cancer metastasis. Citation Format: Yu X, He T, Xu J. The N-terminus of Twist1 is responsible for interacting with transcriptional repressors to promote EMT and metastasis of breast cancer cells. [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 P1-05-02.