Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

IQGAP1 in Podosome /Invadosome is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

Version 1 : Received: 17 November 2016 / Approved: 24 November 2016 / Online: 24 November 2016 (18:02:20 CET)
Version 2 : Received: 6 January 2017 / Approved: 9 January 2017 / Online: 9 January 2017 (03:21:17 CET)
Version 3 : Received: 16 January 2017 / Approved: 16 January 2017 / Online: 16 January 2017 (10:30:48 CET)

A peer-reviewed article of this Preprint also exists.

Rotoli, D.; Pérez-Rodríguez, N.D.; Morales, M.; Maeso, M.C.; Ávila, J.; Mobasheri, A.; Martín-Vasallo, P. IQGAP1 in Podosomes/Invadosomes Is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status. Int. J. Mol. Sci. 2017, 18, 150. Rotoli, D.; Pérez-Rodríguez, N.D.; Morales, M.; Maeso, M.C.; Ávila, J.; Mobasheri, A.; Martín-Vasallo, P. IQGAP1 in Podosomes/Invadosomes Is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status. Int. J. Mol. Sci. 2017, 18, 150.

Abstract

Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signalling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumours, suggesting a role for this protein in cell proliferation, transformation and invasion. IQGAP1 has been identified as a marker of amplifying cancer cells in GBMs. To determine the involvement of IQGAP1 in the onco-biology of GBM, we performed immunohistochemical confocal microscopical analysis of the IQGAP1 protein in human GBM tissue samples using cell type-specific markers. IQGAP1 immunostaining and subcellular localization was heterogeneous; the protein was located in the plasma membrane and, at variable levels, in nucleus and/or cytosol. Moreover, IQGAP1 positive staining was found in podosome/invadopodia-like structures. IQGAP1+ staining was observed in neurons (Map2+ cells), in cancer stem cells (CSC; nestin+) and in several macrophages (CD31+ or Iba1+). Our results indicate that the IQGAP1 protein is involved in normal cell physiology and also in oncologic processes.

Keywords

IQGAP1; GBM; scaffold protein; podosome/invadosome

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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