Abstract B69: SHP2 as a novel therapeutic target for triple-negative breast cancer

Abstract

The basal-type/triple-negative breast cancer (BTBC) has the worst clinical outcome primarily because of its invasive nature and lack of targeted therapy. In addition, BTBC is more prevalent in younger African-American women. Therefore, there is an urgent need for discovering and characterizing potential drug targets for BTBC. In this study, we have focused on the Src homology phosphotyrosyl phosphatase 2 (SHP) which seems to play critical roles in promoting BTBC. The major reason for focusing on SHP2 is its positive role in mitogenic and cell survival signaling induced by receptor tyrosine kinases such as EGFR (HER1), PDGFR, IGF-1R, and the cytoplasmic tyrosine kinase Src, which are known to be elevated in BTBC. Here, we have shown that the SHP2 protein is elevated in approximately seventy percent of BTBC tumors, and is highly correlated with overexpression of the EGFR (HER1), suggesting their potential synergistic role to promote BTBC. Functional studies demonstrated that SHP2 is essential for EGF-induced mitogenic and cell survival signaling and for maintenance of the transformed phenotype in BTBC cells. More dramatic was that the invasive phenotype of BTBC cells in 3D matrigel was completely blocked by inhibition of SHP2, suggesting that the invasive property of these cells is dependent on SHP2. Even more dramatic was that the tumorigenic and metastatic potential of BTBC cells was abolished by SHP2 inhibition. These results show that SHP2 has untapped potential to serve as a drug target in BTBC. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B69.