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Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways

Kim, S; Choy, C; kim, H; Lee, JY; Williams, DM; Palethorpe, D; Fellows, G; Wright, AJ; Laing, K; Bridges, LR; et al. Kim, S; Choy, C; kim, H; Lee, JY; Williams, DM; Palethorpe, D; Fellows, G; Wright, AJ; Laing, K; Bridges, LR; Howe, FA (2013) Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways. Endocrine Related Cancer, 21. 85 - 99. ISSN 1351-0088 https://doi.org/10.1530/ERC-13-0181
SGUL Authors: Kim, Soo-Hyun

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Abstract

Anosmin-1, encoded by the KAL1 gene, is an extracellular matrix (ECM)-associated protein which plays essential roles in the establishment of olfactory and GNRH neurons during early brain development. Loss-of-function mutations of KAL1 results in Kallmann syndrome with delayed puberty and anosmia. There is, however, little comprehension of its role in the developed brain. As reactivation of developmental signal pathways often takes part in tumorigenesis, we investigated if anosmin-1-mediated cellular mechanisms associated with brain tumors. Our meta-analysis of gene expression profiles of patients' samples and public microarray datasets indicated that KAL1 mRNA was significantly upregulated in high-grade primary brain tumors compared with the normal brain and low-grade tumors. The tumor-promoting capacity of anosmin-1 was demonstrated in the glioblastoma cell lines, where anosmin-1 enhanced cell motility and proliferation. Notably, anosmin-1 formed a part of active β1 integrin complex, inducing downstream signaling pathways. ShRNA-mediated knockdown of anosmin-1 attenuated motility and growth of tumor cells and induced apoptosis. Anosmin-1 may also enhance the invasion of tumor cells within the ECM by modulating cell adhesion and activating extracellular proteases. In a mouse xenograft model, anosmin-1-expressing tumors grew faster, indicating the role of anosmin-1 in tumor microenvironment in vivo. Combined, these data suggest that anosmin-1 can facilitate tumor cell proliferation, migration, invasion, and survival. Therefore, although the normal function of anosmin-1 is required in the proper development of GNRH neurons, overexpression of anosmin-1 in the developed brain may be an underlying mechanism for some brain tumors.

Item Type: Article
Additional Information: Made available online as an Accepted Preprint 4 November 2013. © 2014 The authors. This work is licensed under a Creative Commons Attribution 3.0 Unported License see http://creativecommons.org/licenses/by/3.0/deed.en_GB
Keywords: anosmin-1, Kallmann syndrome, brain tumor, integrins, matrix metalloproteinases, meta-analysis, tumor microenvironment
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: Endocrine Related Cancer
ISSN: 1351-0088
Dates:
DateEvent
20 December 2013Published
Web of Science ID: FDC398C6-41C9-4D34-BC74-939E5CD88AEA
URI: http://sgultest.da.ulcc.ac.uk/id/eprint/105439
Publisher's version: https://doi.org/10.1530/ERC-13-0181

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