Expression pattern of the scaffold protein IQGAP1 in lung cancer

Nakamura, Hiroki; Fujita, Koji; Nakagawa, Hitomi; Kishi, Fukuko; Takeuchi, Atsushi; Idiris, Aute; Kato, Harubumi

doi:10.3892/or.13.3.427

Cited by 20 publications

(22 citation statements)

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“…Although an increasing number of studies has aimed to elucidate the expression of IQGAP1 in various types of cancer, including lung cancer (21), endometrial cancer (22), ovarian cancer (23), gastric cancer (24), colon cancer (25), hepatic carcinoma (26), breast cancer (27) and even glioma (28), the molecular roles of IQGAP1 remain to be understood and the correlation between clinical outcomes and IQGAP1 expression in human malignant tumors require further investigation. The present study indicated that IQGAP1-siRNA inhibited the proliferation and metastasis of U251 and U373 glioma cells.…”

Section: Discussionmentioning

confidence: 99%

IQGAP1-siRNA inhibits proliferation and metastasis of U251 and U373 glioma cell lines

Diao

Liu

Zhang

et al. 2017

Molecular Medicine Reports

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IQ motif containing GTPase activating protein 1 (IQGAP1) is a scaffold protein, which is aberrantly expressed in several tumor types and is closely associated with the development, metastasis and prognosis of cancer. Several studies have demonstrated that IQGAP1 has broad prospects in the basic and clinical research of tumors. The present study aimed to explore the effects of IQGAP1-small interfering (si) NA on the proliferation and metastasis of U251 and U373 glioma cell lines, which markedly expressed IQGAP1. The human glioma cell lines (U251 and U373) were transfected with siRNA and transfection efficacy was confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Cell proliferation was detected using the Cell Counting kit-8, and cell metastasis capabilities were detected using cell adhesion, migration and invasion assays. In addition, the expression levels of several tumor-associated genes were determined by RT-qPCR and western blotting. The results indicated that IQGAP1 was expressed at higher levels in glioma tissues compared with in normal brain tissues. IQGAP1-siRNA significantly inhibited cell proliferation, and cell adhesion, migration and invasion. Furthermore, the expression levels of matrix metalloproteinase (MMP)2, Snail, MMP9, fibronectin 1 and Twist were suppressed, and E-cadherin was upregulated in response to siRNA-IQGAP1. The present study identified the function of IQGAP1 in glioma cell biology, and indicated that it may be considered a novel target for glioma treatment.

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Section: Discussionmentioning

confidence: 99%

IQGAP1-siRNA inhibits proliferation and metastasis of U251 and U373 glioma cell lines

Diao

Liu

Zhang

et al. 2017

Molecular Medicine Reports

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“…Over-expression and membrane localization of IQGAP, which is often found at the invasive front of tumors, is associated with poorly differentiated cancer cells and decreased survival in ovarian, lung, colon, endometrial, gastric, and gliomal cancers [70][71][72][73][74][75]. In addition, a 15q26 amplification in gastric cancer cell lines was shown to result in increased IQGAP level [76].…”

Section: Cytoplasmic Accumulation Of α-Cateninmentioning

confidence: 99%

Bench to bedside and back again: Molecular mechanisms of α-catenin function and roles in tumorigenesis

Benjamin

Nelson

2008

Seminars in Cancer Biology

107

115

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The cadherin/catenin complex, comprised of E-cadherin, β-catenin and α-catenin, is essential for initiating cell-cell adhesion, establishing cellular polarity and maintaining tissue organization. Disruption or loss of the cadherin/catenin complex is common in cancer. As the primary cell-cell adhesion protein in epithelial cells, E-cadherin has long been studied in cancer progression. Similarly, additional roles for β-catenin in the Wnt signaling pathway has led to many studies of the role of β-catenin in cancer. Alpha-catenin, in contrast, has received less attention. However, recent data demonstrate novel functions for α-catenin in regulating the actin cytoskeleton and cell-cell adhesion, which when perturbed could contribute to cancer progression. In this review, we use cancer data to evaluate molecular models of α-catenin function, from the canonical role of α-catenin in cell-cell adhesion to non-canonical roles identified following conditional α-catenin deletion. This analysis identifies α-catenin as a prognostic factor in cancer progression.

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“…IQGAP1 has attracted attention from cancer and developmental biologists because IQGAP1 expression appears to play an opposite role in normal development and in cancer progression. Studies with human tumor tissues have suggested that IQGAP1 is an oncogene, which is overexpressed in a number of human solid neoplasms, including cancers of the colon, ovaries, stomach, and breast as well as glioblastoma (25)(26)(27)(28)(29). Functional studies have established the fact that IQGAP1 interacts with and regulates the actin-Cdc42/Rac1-mitogen-activated protein kinase pathway, thus contributing to its role in cell migration and invasion (19).…”

Section: Introductionmentioning

confidence: 99%

Genetic variants at the miR-124 binding site on the cytoskeleton-organizing IQGAP1 gene confer differential predisposition to breast cancer

et al. 2011

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Abstract. IQGAP1 knockout mice develop gastric cancer, but the IQGAP1 protein is associated with some advanced-stage human cancers. IQGAP1 expression is regulated by a microRNA, miR-124, through a binding site at the 3'-untranslated region, where a single nucleotide polymorphism (SNP) exists in the core binding region. We asked whether IQGAP1 expression is associated with breast cancer development and whether genetic variants at the miR-124 binding site are important. We genotyped the IQGAP1 SNP rs1042538 A/T in 1,541 breast cancer cases and 1,598 controls and analyzed the frequency of the variant and interactions with major risk factors in these populations. We also measured the expression of IQGAP1 at both mRNA and protein levels in different IQGAP1 genotypes. The IQGAP1 TT genotype, compared with the AA genotype, was associated with a significantly lower risk of developing breast cancer [P=0.049, odds ratio (OR), 0.78; 95% confidence interval (CI), 0.61-0.99]. In case-only analyses, the TT, compared with the AA, genotype was associated with progesterone receptor-positive subjects (OR, 1.35; 95% CI, 1.00-1.83). The expression levels of IQGAP1 protein were significantly higher in the TT genotype compated to the AA genotype. The presence of SNPs at the miR-124 binding site may be a marker for predicting breast cancer risk and prognosis.

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Expression pattern of the scaffold protein IQGAP1 in lung cancer

Cited by 20 publications

References 0 publications

IQGAP1-siRNA inhibits proliferation and metastasis of U251 and U373 glioma cell lines

IQGAP1-siRNA inhibits proliferation and metastasis of U251 and U373 glioma cell lines

Bench to bedside and back again: Molecular mechanisms of α-catenin function and roles in tumorigenesis

Genetic variants at the miR-124 binding site on the cytoskeleton-organizing IQGAP1 gene confer differential predisposition to breast cancer

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