Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways
| Autor: | David Palethorpe, Jiyoung Lee, Greg A. Fellows, Haseong Kim, Soo-Hyun Kim, Leslie R Bridges, Franklyn A. Howe, Catherine T Choy, Alan J. Wright, David M. Williams, Ken Laing |
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| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Endocrinology Diabetes and Metabolism Integrin Brain tumor Apoptosis Nerve Tissue Proteins Mice SCID medicine.disease_cause Anosmin-1 Extracellular matrix Mice Endocrinology Cell Movement Mice Inbred NOD Cell Line Tumor medicine Animals Humans tumor microenvironment Cell adhesion Oligonucleotide Array Sequence Analysis Extracellular Matrix Proteins Tumor microenvironment biology Brain Neoplasms Reverse Transcriptase Polymerase Chain Reaction Integrin beta1 Research Kallmann syndrome matrix metalloproteinases medicine.disease Molecular biology Cell biology meta-analysis Oncology integrins biology.protein Heterografts RNA Female anosmin-1 Signal transduction Glioblastoma Carcinogenesis brain tumor Signal Transduction |
| Zdroj: | Endocrine-Related Cancer |
| ISSN: | 1479-6821 1351-0088 |
| DOI: | 10.1530/erc-13-0181 |
| Popis: | Anosmin-1, encoded by theKAL1gene, 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 ofKAL1results 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 thatKAL1mRNA 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 microenvironmentin 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. |
| Databáze: | OpenAIRE |
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