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Open AccessArticle

Role of GOLPH3 and TPX2 in Neuroblastoma DNA Damage Response and Cell Resistance to Chemotherapy

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Laboratorio Cellule Staminali Post Natali e Terapie Cellulari, IRCCS Giannina Gaslini, 16147 Genova, Italy
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Divisione di Oncologia, IRCCS Giannina Gaslini, 16147 Genova, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(19), 4764; https://doi.org/10.3390/ijms20194764
Received: 30 August 2019 / Revised: 16 September 2019 / Accepted: 20 September 2019 / Published: 25 September 2019
(This article belongs to the Section Molecular Oncology)
Neuroblastoma (NB) is an aggressive, relapse-prone infancy tumor of the sympathetic nervous system and is the leading cause of death among preschool age diseases, so the search for novel therapeutic targets is crucial. Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development, and in the DNA damage response, of various human cancers. Golgi dispersal is a common feature of DNA damage response in mammalian cells. Understanding how cells react to DNA damage is essential in order to recognize the systems used to escape from elimination. We induced DNA damage in two human neuroblastoma cell lines by curcumin. The exposure of neuroblastoma cells to curcumin induced: (a) up-regulation of GOLPH3+ cells; (b) augmentation of double-strand breaks; (c) Golgi fragmentation and dispersal throughout the cytoplasm; (d) increase of apoptosis and autophagy; (e) increased expression of TPX2 oncoprotein, able to repair DNA damage. Primary neuroblastoma samples analysis confirmed these observations. Our findings suggest that GOLPH3 expression levels may represent a clinical marker of neuroblastoma patients’ responsiveness to DNA damaging therapies—and of possible resistance to them. Novel molecules able to interfere with GOLPH3 and TPX2 pathways may have therapeutic benefits when used in combination with standard DNA damaging therapeutic agents in neuroblastoma View Full-Text
Keywords: Neuroblastoma; DNA-damage; GOLPH3; resistance to drugs; TPX2; autophagy Neuroblastoma; DNA-damage; GOLPH3; resistance to drugs; TPX2; autophagy
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    Doi: 10.5281/zenodo.3381842
    Description: Supplementary Figure 1. Immunofluorescence analysis of non tumoral control HEK-293 cells cultured with 20 µM curcumin 48 hours using anti-γH2AX (red). Cells were counterstained with DAPI to visualize nuclei (blue). Untreated cells were cultured with 0.1% DMSO. (Magnification 40x). Supplementary Figure 2. Immunofluorescence analysis of IMR-32 and SH-SY5Y cells cultured respectively with 300 nM or 500 nM Rapamycin, with 2 nM or 3.5 nM Bortezomib and with 0.02 µM or 0.05 µM Colchicine for 48 hours using anti-GOLPH3 (green) and anti-γH2AX (red) and compared to untreated cells. Cells were counterstained with DAPI to visualize nuclei (blue). (Magnification 40x). In green and red boxes are reported the percentages of GOLPH3 and γH2AX positive cells respectively. Data are representative of three independent experiments ± S.D.
MDPI and ACS Style

Ognibene, M.; Podestà, M.; Garaventa, A.; Pezzolo, A. Role of GOLPH3 and TPX2 in Neuroblastoma DNA Damage Response and Cell Resistance to Chemotherapy. Int. J. Mol. Sci. 2019, 20, 4764.

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