Alterations in IQGAP1 expression and localization in colorectal carcinoma and liver metastases following oxaliplatin‑based chemotherapy

Rotoli,Deborah; Morales,Manuel; Maeso,María Del Carmen; García,María Del Pino; Gutierrez,Ricardo; Valladares,Francisco; Ávila,Julio; Díaz‑Flores,Lucio; Mobasheri,Ali; Martín‑Vasallo,Pablo

doi:10.3892/ol.2017.6525

Alterations in IQGAP1 expression and localization in colorectal carcinoma and liver metastases following oxaliplatin‑based chemotherapy

Authors:
- Deborah Rotoli
- Manuel Morales
- María Del Carmen Maeso
- María Del Pino García
- Ricardo Gutierrez
- Francisco Valladares
- Julio Ávila
- Lucio Díaz‑Flores
- Ali Mobasheri
- Pablo Martín‑Vasallo
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Affiliations: Laboratory of Developmental Biology, UD‑Biochemistry and Molecular Biology and Centre for Biomedical Research of The Canary Islands, University of La Laguna, 38206 La Laguna, Canary Islands, Spain, Service of Medical Oncology, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Canary Islands, Spain, Service of Pathology, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Canary Islands, Spain, Department of Pathology, Hospiten Rambla, 38001 Santa Cruz de Tenerife, Canary Islands, Spain, Department of Pathology, School of Medicine, University of La Laguna, 38201 La Laguna, Canary Islands, Spain, Department of Veterinary Preclinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK
Published online on: July 5, 2017 https://doi.org/10.3892/ol.2017.6525
Pages: 2621-2628
Copyright: © Rotoli et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

IQGAP1 is a scaffolding protein that serves a key role in cell dynamics by integrating internal and external stimuli to distinct signal outputs. Previous studies have identified several genes that are significantly up‑ or downregulated in the peripheral white cells (PWCs) of patients with colorectal adenocarcinoma (CRC), who underwent oxaliplatin‑based chemotherapy (CT). In addition, screening studies have reported that IQ‑motif containing GTPase activating protein 1 (IQGAP1) transcriptional expression levels varied from ‘off’ to ‘on’ following oxaliplatin CT. In order to determine if variations previously described in PWCs are able to be observed at the protein level in tumors and in metastases following CT, the present study performed an immunohistochemical analysis of IQGAP1 in CRC and primary metastases. IQGAP1 expression was observed in the nuclear envelope and in lateral cell membranes and cytoplasm in normal colon tissue. However, in tumor tissue, cells exhibited a diffuse pattern, with variable expression levels of staining in the nuclear membrane and cytoplasm, with the highest expression intensity observed at the invasive front. In healthy and metastasized liver tissue and in the metastases themselves, expression levels varied from cell to cell from no expression to a high level. In the majority of cells, IQGAP1 co‑localized with microtubules at the cytoplasmic face of the nuclear envelope. Strong positive expression was observed in areas of the lesion where cells were detaching from the lesion into the lumen. Despite the homogeneous IQGAP1 staining pattern observed in healthy colon tissue sections, CRC demonstrated heterogeneity in staining, which was more marked in metastasized liver tissue resected following CT. However, the most notable findings were the observed effects on the cellular and subcellular distribution and its implications for cancer biology. These results suggest that IQGAP1 may be a putative biomarker, a candidate for clinical diagnostics and a potential novel target for anti‑cancer therapeutics.

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