Abstract A49: The ERK/MAPK scaffold IQGAP1 is a tumor-selective target

Abstract To advance insight into skin biology and pathophysiology, our lab has focused on understanding how the normal processes of cell division and migration are regulated and how they become dysregulated in pathological states, including cancer. One particular pathway of interest in the lab is the extracellular-regulated kinase/mitogen-activated protein kinase (Erk/MAPK) pathway. This highly conserved pathway is critical to epidermal homeostasis and tumorigenesis, but its mechanisms of action remain unclear. This research explores how the Erk/MAPK-interacting protein IQGAP1 mediates signaling in tumorigenesis. IQGAP1 physically interacts with canonical Erk/MAPK pathway members in order to precisely modulate their signal output and in its absence, signaling through this pathway is severely diminished. We recently found that depleting expression of IQGAP1, a Mek- and Erk-binding MAPK-IP, exerted no effect on normal tissue but effectively blocked invasive neoplasia. We are currently working to define the functional domains of IQGAP1 required for Erk MAPK-driven epidermal neoplasia. These efforts will help identify potentially important and therapeutically relevant neoplasia-selective interactions of IQGAP1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A49.