RT info:eu-repo/semantics/article
T1 Alterations in IQGAP1 expression and localization in colorectal carcinoma and liver metastases following oxaliplatin based chemotherapy
A1 Morales González, Manuel José
A1 ROTOLI, DEBORAH
A1 MAESO, MARÍA DEL CARMEN
A1 GARCÍA, MARÍA DEL PINO
A1 GUTIERREZ, RICARDO
A1 VALLADARES, FRANCISCO
A1 ÁVILA, JULIO
A1 DÍAZ-FLORES, LUCIO
A1 MOBASHERI, ALI
A1 MARTÍN-VASALLO, PABLO
A2 Medicina InternaDermatología y Psiquiatría
K1 colorectal cancer
K1 oxaliplatin
K1 IQGAP1
K1 scaffold protein
AB . IQGAP1 is a scaffolding protein that serves a keyrole in cell dynamics by integrating internal and externalstimuli to distinct signal outputs. Previous studies have identified several genes that are significantly up‑ or downregulatedin the peripheral white cells (PWCs) of patients with colorectaladenocarcinoma (CRC), who underwent oxaliplatin‑basedchemotherapy (CT). In addition, screening studies havereported 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 atthe protein level in tumors and in metastases following CT, thepresent study performed an immunohistochemical analysis ofIQGAP1 in CRC and primary metastases. IQGAP1 expression was observed in the nuclear envelope and in lateral cellmembranes and cytoplasm in normal colon tissue. However,in tumor tissue, cells exhibited a diffuse pattern, with variableexpression levels of staining in the nuclear membrane andcytoplasm, with the highest expression intensity observed at theinvasive front. In healthy and metastasized liver tissue and inthe metastases themselves, expression levels varied from cell tocell from no expression to a high level. In the majority of cells,IQGAP1 co‑localized with microtubules at the cytoplasmicface of the nuclear envelope. Strong positive expression wasobserved in areas of the lesion where cells were detaching fromthe lesion into the lumen. Despite the homogeneous IQGAP1staining pattern observed in healthy colon tissue sections,CRC demonstrated heterogeneity in staining, which was moremarked in metastasized liver tissue resected following CT.However, the most notable findings were the observed effectson the cellular and subcellular distribution and its implicationsfor cancer biology. These results suggest that IQGAP1 may bea putative biomarker, a candidate for clinical diagnostics and apotential novel target for anti-cancer therapeutics.
YR 2017
FD 2017
LK http://riull.ull.es/xmlui/handle/915/40043
UL http://riull.ull.es/xmlui/handle/915/40043
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 28-nov-2024