Abstract 3330: HER2 overexpression induces membrane deformation that increases cell motility

Abstract

Abstract Approximately 20% of breast cancers (BC) are characterized by the gene amplification and overexpression of HER2, a member of the ErbB/HER receptor family. While targeted therapies against HER2 effectively delay disease progression in this BC subtype, details of how overexpressed HER2s drive these tumors to malignancy are still unclear. To better understand this process, we investigated various cellular responses to HER2 overexpression in individual live cells. We developed novel single receptor diffusion analyses that determine the activation status of HER2 by diffusivity, to estimate average HER2 activity per single cell. Surprisingly, we found HER2 overexpression induces membrane deformation, which depends only on the HER2 density, but not the receptor activation status. Moreover, this membrane deformation lowers the available surface area for formation of focal adhesion sites, resulting in reduced cell adhesion and increased cell motility. These findings suggest there are signaling-independent roles of HER2 overexpression in disease progression of HER2 positive BCs. Citation Format: Inhee Chung, Mike Reichelt, Donald Dowbenko, Ira Mellman, Mark Sliwkowski. HER2 overexpression induces membrane deformation that increases cell motility. [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 3330. doi:10.1158/1538-7445.AM2014-3330