Abstract 2093: LPP promotes ErbB2 overexpressing breast cancer cell migration, invasion and metastasis

Abstract

Abstract Metastatic breast cancer remains a major hurdle to the successful treatment of this disease. Overexpression of the HER2/ErbB2 receptor tyrosine kinase in breast cancer is associated with metastatic disease and correlates with poor patient prognosis. Growing evidence demonstrates that TGFβ can potentiate ErbB2 signaling to enhance the invasive and metastatic behavior of breast cancer cells. Nonetheless, the mechanisms underlying the synergy between TGFβ and ErbB2 signaling pathways remain to be elucidated. We previously identified Lipoma Preferred Partner (LPP) as an indispensable mediator of TGFβ-induced migration, invasion and focal adhesion turnover of ErbB2-expressing breast cancer cells. Furthermore, we established domains within LPP that are required for its localization to focal adhesions and for its interaction with α-Actinin, an actin cross-linking protein, to promote cell migration and invasion. Herein, we examine the requirement of LPP in tumorigenesis and metastasis formation. We observe that LPP is dispensable for primary tumor growth. Nonetheless, the loss of LPP leads to decrease in spontaneous lung metastasis formation of ErbB2-expressing breast cancer cells injected into the mammary fat pads of mice. Furthermore, we observe that LPP is a critical determinant for efficient dissemination of breast cancer cells. We show that shRNA-mediated reduction of LPP significantly impairs pulmonary metastasis formation in experimental metastasis tail vein assay. Overall, we have identified LPP as a novel mediator that integrates TGFβ and ErbB2 signaling to promote the migration, invasion and metastasis of breast cancer cells. We identify LPP as a pro-metastatic mediator of ErbB2 overexpressing breast cancer cells and a potential new biomarker of metastatic breast cancer. Citation Format: Elaine Ngan, Peter M. Siegel. LPP promotes ErbB2 overexpressing breast cancer cell migration, invasion and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2093. doi:10.1158/1538-7445.AM2014-2093