Abstract 1079: Identification of autocrine motility factor (AMF) receptor, HER2 (ErbB2) in breast cancer cells

Overexpression of HER2 (ErbB2) oncoprotein is associated with approximately 25% of aggressive breast carcinoma. Although a humanized monoclonal antibody (Trastuzumab) against HER2 is currently considered one of the most effective treatments, a significant number of patients are initially or eventually become resistant to Trastuzumab based therapy. Here, we demonstrate that secreted phosphoglucose isomerase (PGI)/ autocrine motility factor (AMF), an orphan -CXXC- cytokine directly binds to HER2 and activates PI3K and MAPK through HER2 autophosphorylation, and also induces immediately HER2 cleavage in metalloprotease dependent fashion. We therefore speculate that AMF/HER2 signaling pathways play a physiological role in HER2 overexpressing breast cancer cells and contribute to Trastuzumab resistance and propose that AMF can be a novel therapeutic target in Trastuzumab resistant breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1079. doi:1538-7445.AM2012-1079