Abstract 4602: Abi1 promotes breast cancer progression by regulating cell-matrix adhesion

Abstract

Abstract Breast cancer is one of the most common diagnosed cancers in the United States. There will be approximately 266,120 new breast cancer cases in the U.S. and over 40,000 patients are predicted to die from the malignant progression of their breast cancer tumors in 2018. Traditional therapeutic methods of the invasive breast cancer include surgery accompanied by chemotherapy. However, following the initial therapy patients often relapse and eventually die from tumor metastasis. Abl interactor 1, or Abi1, is an adaptor protein which regulates actin polymerization through participation in WAVE (Wiscott-Aldrich syndrome protein family verprolin homologous) complex. The WAVE regulatory complex (also called WRC), regulates actin based cellular behavior, such as cellular adhesion and cell migration, by activating Arp2/3 complex and promoting actin polymerization. Previous studies indicated the direct interaction between integrin α4 and Abi1, which suggests a potential role of Abi1 in regulating cell-matrix adhesion signaling by involved in the inside-out integrin signaling pathways. In order to test the above hypothesis, we developed two genetic engineered Abi1 knocked-out breast cell lines from either HER2+ breast cancer cell line SKBR3 or normal breast epithelial cell line MCF10A by using CRISPR-Cas9 technique. After confirming inactivation of Abi1 gene by Western blotting, DNA and RNA sequencing, cells were harvested and analyzed for integrins levels. Western blotting results indicated dysregulation of multiple integrins in the Abi1 knock-out cell lines. The results from subsequent immunofluorescence experiments of the Abi1 knock-out cell lines also suggested changes in cell-matrix adhesion signaling using staining for scaffold protein paxillin and phosphorylated Focal-Adhesion-Kinase (FAK) as readouts. Our findings suggest that Abi1 might functions as a key regulator in breast cancer tumor progression by playing an important role in regulating signal pathways in cell-matrix adhesion. Supported by the Carol Baldwin Foundation of CNY, and in part by NIH-NCI grant No. R01 CA161018. Citation Format: Xiang Li, Angelina Regua, Gennady Bratslavsky, Vladimir A. Kuznetsov, Leszek Kotula. Abi1 promotes breast cancer progression by regulating cell-matrix adhesion [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 4602.