Abstract 2638: The BCAR3/Cas/c-Src signaling node in breast cancer progression.

Abstract

Abstract Despite advances in early detection and improved adjuvant therapies, breast cancer remains the second leading cause of cancer death among women mainly due to metastatic spread of the disease. The ability of cancer cells to migrate and invade is important in the process of metastasis. Studies have shown that the adaptor protein Breast Cancer Antiestrogen Resistance 3 (BCAR3) is highly expressed in invasive breast cancer cell lines and functions as a positive regulator of migration and invasion. To date, BCAR3 has only one clearly established binding partner in breast cancer cells, the adaptor protein, p130Cas (Cas). Studies of human breast tumors have shown a positive correlation between high levels of Cas protein expression and poor clinical outcome in patients (Dorssers LC et al, 2004). Additionally, the protein tyrosine kinase c-Src is a C-terminal binding partner of Cas. c-Src kinase activity promotes enhanced Cas signaling and is associated with breast cancer progression and poor clinical outcome (Blscardi JS et al, 1999). These data suggest a critical role for the BCAR3/Cas/c-Src signaling node in breast tumor progression. We hypothesize that enhanced signaling through the BCAR3/Cas/c-Src network in breast epithelial cells is critical for the transition to an invasive cancer cell phenotype. In this work, we compared the relationship between these proteins in non-tumorigenic mammary epithelial cells (MCF10A) and invasive breast cancer cells (BT549 and MDA-MB-231). As is the case for invasive breast cancer cells, we found that the majority of BCAR3 in MCF10A breast epithelial cells is in complex with Cas. However, less Cas is found in association with c-Src in MCF10A cells compared to more invasive breast cancer cells. These finding suggest that despite some similarities in BCAR3, Cas, and c-Src signaling between non-tumorigenic and invasive breast cancer cells, both the physical interplay between these proteins and the signaling pathways activated downstream become dysregulated as non-tumorigenic cells progress to a fully oncogenic state. A better understanding of BCAR3/Cas/c-Src signaling in non-tumorigenic versus invasive breast tumor cells is necessary to determine whether this signaling network contributes to breast tumor progression and metastasis. Citation Format: Allison M. Batties, Michael S. Guerrero, Ashley L. Wilson, Keena S. Thomas, Amy H. Bouton. The BCAR3/Cas/c-Src signaling node in breast cancer progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2638. doi:10.1158/1538-7445.AM2013-2638