Abstract | PURPOSE: 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. EXPERIMENTAL DESIGN: We examined IQGAP1 copy gain and its relationship with clinicopathologic outcomes of thyroid cancer and investigated its role in cell invasion and molecules involved in the process. RESULTS: We found IQGAP1 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. IQGAP1 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 BRAF mutation-positive PTC (P = 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. CONCLUSIONS: 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.
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Authors | Zhi Liu, Dingxie Liu, Ermal Bojdani, Adel K El-Naggar, Vasily Vasko, Mingzhao Xing |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 16
Issue 24
Pg. 6009-18
(Dec 15 2010)
ISSN: 1557-3265 [Electronic] United States |
PMID | 20959410
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | ©2010 AACR. |
Chemical References |
- Cadherins
- IQ motif containing GTPase activating protein 1
- RNA, Small Interfering
- ras GTPase-Activating Proteins
- Phosphatidylinositol 3-Kinases
- Oncogene Protein v-akt
- Extracellular Signal-Regulated MAP Kinases
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Topics |
- Cadherins
(metabolism)
- Carcinoma, Papillary, Follicular
(genetics, pathology)
- Cells, Cultured
- Extracellular Signal-Regulated MAP Kinases
(metabolism)
- Female
- Gene Dosage
- Gene Expression Regulation, Neoplastic
(drug effects)
- Gene Knockdown Techniques
- Humans
- Male
- Mutation
(physiology)
- Neoplasm Invasiveness
- Oncogene Protein v-akt
(metabolism, physiology)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Protein Binding
- RNA, Small Interfering
(pharmacology)
- Thyroid Neoplasms
(genetics, pathology)
- ras GTPase-Activating Proteins
(genetics, metabolism, physiology)
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