Abstract P2-07-02: IGF1R/FAK crosstalk is essential for epithelial-to-mesenchymal transition (EMT), migration, and invasion of TNBC cells

Abstract

Abstract Triple negative breast cancers (TNBCs) are highly metastatic and deadly tumors that currently lack effective prevention and treatment options. Insulin-like growth factor 1 receptor (IGF1R) and focal adhesion kinase (FAK) both play a role in several developmental processes, and both IGF1R and FAK signaling pathways have been linked to a number of common pathological diseases, including breast cancers. In particular, overexpression of IGF1R and FAK are closely associated with metastatic breast tumors. However, the relationship between the IGF1R and FAK signaling cascades in metastatic TNBCs remain largely unknown. The present study aimed to investigate the interrelationship between IGF1R and FAK crosstalk in regulating the malignant properties of TNBC cells. Using stable small hairpin RNA (shRNA)-mediated IGF1R silencing and stable full-length IGF1R plasmid over-expression methods, we demonstrated that IGF1R was essential for maintaining mesenchymal morphologies of TNBC and regulating the expression of EMT markers, including vimentin, ZEB-1, Snail-1, E-cadherin, ZO-1, and claudin-1. Using colony formation, spheroid migration, and Matrigel invasion assays, we further showed that IGF1R promoted migratory and invasive TNBC phenotypes, including increased colony formation, cell migration, and invasion. Most importantly, IGF1R-mediated migration and invasion required FAK activation and could be augmented using pharmacological inhibitors of FAK. Our findings in TNBC cells demonstrate a novel role of the IGF1R/FAK signaling pathway in regulating critical processes involved in the metastatic cascade. These results may improve the current understanding of the basic molecular mechanisms of TNBC metastasis and provide a strong rationale for co-targeting of IGF1R and FAK as therapy for mesenchymal TNBCs. Citation Format: LaTonia D Taliaferro-Smith, Elaine Oberlick, Tongrui Liu, Tanisha Z McGlothen, Ruth O'Regan. IGF1R/FAK crosstalk is essential for epithelial-to-mesenchymal transition (EMT), migration, and invasion of TNBC cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-07-02.