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

Rotoli, D, Morales, M, Del Carmen Maeso, M, Del Pino Garcia, M, Gutierrez, R, Valladares, F, Avila, J, Diaz-Flores, L, Mobasheri, Ali and Martin-Vasallo, P (2017) Alterations in IQGAP1 expression and localization in colorectal carcinoma and liver metastases following oxaliplatin‑based chemotherapy Oncology Letters, 14 (3). pp. 2621-2628.

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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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
NameEmailORCID
Rotoli, DUNSPECIFIEDUNSPECIFIED
Morales, MUNSPECIFIEDUNSPECIFIED
Del Carmen Maeso, MUNSPECIFIEDUNSPECIFIED
Del Pino Garcia, MUNSPECIFIEDUNSPECIFIED
Gutierrez, RUNSPECIFIEDUNSPECIFIED
Valladares, FUNSPECIFIEDUNSPECIFIED
Avila, JUNSPECIFIEDUNSPECIFIED
Diaz-Flores, LUNSPECIFIEDUNSPECIFIED
Mobasheri, Alia.mobasheri@surrey.ac.ukUNSPECIFIED
Martin-Vasallo, PUNSPECIFIEDUNSPECIFIED
Date : 26 August 2017
Identification Number : 10.3892/ol.2017.6525
Copyright Disclaimer : Copyright 2017 Spandidos Publications
Uncontrolled Keywords : colorectal cancer, oxaliplatin, IQGAP1, scaffold protein
Depositing User : Melanie Hughes
Date Deposited : 26 May 2017 17:16
Last Modified : 22 Sep 2017 09:31
URI: http://epubs.surrey.ac.uk/id/eprint/841171

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