Abstract 162: ASB13 inhibits breast cancer progression and metastasis through SNAI2 degradation and transcriptional regulation of YAP

Abstract

Abstract Metastasis is responsible for the majority of cancer-related deaths. The transcription factor SNAI2 promotes metastasis by facilitating tumor cell invasion and tumor initiating activity. However, its post-translational regulation is less studied. We performed a dual luciferase-based, genome-wide E3 ligase siRNA library screening and identified ASB13 as an E3 ubiquitin ligase that targets SNAI2 for ubiquitination and degradation. ASB13 knockout in breast cancer cells leads to increased cell migration and decreased F-actin polymerization; while overexpression of ASB13 suppresses lung metastasis formed by LM2 cells. Furthermore, we discovered that ASB13 knockout decreases YAP expression, which is dependent on increased SNAI2 protein level. YAP functions as a tumor suppressor gene in breast cancer, as YAP knockout increases tumorsphere formation, anchorage-independent colony formation, and cell migration. Clinical data analysis reveals that ASB13 expression is positively correlated with overall survival in breast cancer patients. These findings establish the ASB13-SNAI2-YAP axis as a regulatory mechanism for breast cancer migration and metastasis. Citation Format: Huijuan Fan, Xuxiang Wang, Wenyang Li, Minhong Shen, Yong Wei, Hanqiu Zheng, Yibin Kang. ASB13 inhibits breast cancer progression and metastasis through SNAI2 degradation and transcriptional regulation of YAP [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 162.