Kif3a is necessary for initiation and maintenance of medulloblastoma
| العنوان: | Kif3a is necessary for initiation and maintenance of medulloblastoma |
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| المؤلفون: | Matthew P. Scott, Eric W. Humke, Monique T. Barakat |
| المصدر: | Carcinogenesis. 34:1382-1392 |
| بيانات النشر: | Oxford University Press (OUP), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Patched Receptors, Patched, Cancer Research, medicine.medical_specialty, animal structures, Antineoplastic Agents, Hormonal, Kruppel-Like Transcription Factors, Kinesins, Mice, Nude, Original Manuscript, Mice, Transgenic, Receptors, Cell Surface, Zinc Finger Protein Gli2, Biology, 3T3 cells, Mice, Cell Line, Tumor, Internal medicine, medicine, Animals, Humans, Hedgehog Proteins, KIF3A, Cilia, Sonic hedgehog, Cerebellar Neoplasms, Wnt Signaling Pathway, Medulloblastoma, Cilium, Wnt signaling pathway, 3T3 Cells, General Medicine, medicine.disease, Cell biology, Patched-1 Receptor, Tamoxifen, stomatognathic diseases, Cell Transformation, Neoplastic, Endocrinology, medicine.anatomical_structure, biology.protein |
| الوصف: | Medulloblastoma (MB) cells arise from granule neuron precursors (GNPs) that have lost growth control. During normal development, GNPs divide in response to Sonic hedgehog (SHH), a ligand that binds to the patched (PTCH) receptor on GNPs. If one copy of the Ptch gene is lost, as in human Gorlin's syndrome and in Ptch(+/-) mice, MBs may form. Proper transduction of the SHH signal critically depends on primary cilia. Loss of primary cilia results in improper signal reception and failure to properly activate SHH target genes. KIF3a, part of a kinesin motor, is required for formation of primary cilia. Here, we use tamoxifen-induced ablation of Kif3a in GNPs of postnatal Ptch(+/-) mouse cerebella to show that KIF3a is necessary for MB formation. To investigate the importance of primary cilia in established tumors, we deleted Kif3a from cultured cells and from tumor cell grafts. The loss of Kif3a from established tumors led to their growth arrest and regression. MBs behave as if they are addicted to the presence of primary cilia. These results underscore the potential utility of agents that disrupt cilia for the treatment of Hh pathway-related MBs. |
| تدمد: | 1460-2180 0143-3334 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b5df996ba9a69338c7a6831174809b0Test https://doi.org/10.1093/carcin/bgt041Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4b5df996ba9a69338c7a6831174809b0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602180 01433334 |
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