Research Projects

The Arginine and Glutamine-rich protein 1 (ARGLU1) and p21-activated kinase 1 (PAK1) are frequently overexpressed in breast tumors and associated with aggressive tumor phenotypes and poor clinical outcomes (1). Estrogen receptor α (ERα) plays a major role in the development of breast tumorigenesis, and its activity is mediated by 17-β estradiol (E2). It is well established that ARGLU1 is required for estrogen receptor-mediated gene transcription and breast cancer cell growth and its depletion impair the anchorage-dependent and -independent colony formation of breast cancer cells (2). This evidence clearly suggests that ARGLU1 might be a novel therapeutic target for the treatment of breast cancer. To address these concerns, based on the preliminary data that researchers have, they propose the concept of combined inhibition of ARGLU1 and p21-activated kinase 1 as a new treatment strategy in breast cancer. Our preliminary data results showed that PAK1 phosphorylation sites on ARGLU1. This result suggests that ARGLU1 is a physiological interacting substrate of PAK1, and this phosphorylation may act as a molecular switch in regulating its activity. Based on this result, we hypothesize that post translational modification of ARGLU1 by PAK1 results in increased activity and thus bringing about more estrogen production in peripheral tissues. Hence, we plan to systematically study the aftermath effect of ARGLU1 post translational modification by PAK1 and explore ways to target this regulatable switch by inhibiting PAK1 kinase.