Data from IQGAP1 Plays an Important Role in the Invasiveness of Thyroid Cancer

Abstract

<div>Abstract<p><b>Purpose:</b> This study was designed to explore the role of IQGAP1 in the invasiveness of thyroid cancer and its potential as a novel prognostic marker and therapeutic target in this cancer.</p><p><b>Experimental Design:</b> We examined <i>IQGAP1</i> copy gain and its relationship with clinicopathologic outcomes of thyroid cancer and investigated its role in cell invasion and molecules involved in the process.</p><p><b>Results:</b> We found <i>IQGAP1</i> copy number (CN) gain ≥3 in 1 of 30 (3%), 24 of 74 (32%), 44 of 107 (41%), 8 of 16 (50%), and 27 of 41 (66%) of benign thyroid tumor, follicular variant papillary thyroid cancer (FVPTC), follicular thyroid cancer (FTC), tall cell papillary thyroid cancer (PTC), and anaplastic thyroid cancer, respectively, in the increasing order of invasiveness of these tumors. A similar tumor distribution trend of CN ≥4 was also seen. <i>IQGAP1</i> copy gain was positively correlated with IQGAP1 protein expression. It was significantly associated with extrathyroidal and vascular invasion of FVPTC and FTC and, remarkably, a 50%–60% rate of multifocality and recurrence of <i>BRAF</i> mutation–positive PTC (<i>P</i> = 0.01 and 0.02, respectively). The siRNA knockdown of IQGAP1 dramatically inhibited thyroid cancer cell invasion and colony formation. Coimmunoprecipitation assay showed direct interaction of IQGAP1 with E-cadherin, a known invasion-suppressing molecule, which was upregulated when IQGAP1 was knocked down. This provided a mechanism for the invasive role of IQGAP1 in thyroid cancer. In contrast, IQGAP3 lacked all these functions.</p><p><b>Conclusions:</b> IQGAP1, through genetic copy gain, plays an important role in the invasiveness of thyroid cancer and may represent a novel prognostic marker and therapeutic target for this cancer. <i>Clin Cancer Res; 16(24); 6009–18. ©2010 AACR</i>.</p></div>