Silencing of Histone Deacetylase 6 Decreases Cellular Malignancy and Contributes to Primary Cilium Restoration, Epithelial-to-Mesenchymal Transition Reversion, and Autophagy Inhibition in Glioblastoma Cell Lines
Alejandro Urdiciain,
Elena Erausquin,
María V. Zelaya,
Idoya Zazpe,
José L. Lanciego,
Bárbara Meléndez,
Juan A. Rey,
Miguel A. Idoate,
Natalia A. Riobo-Del Galdo,
Javier S. Castresana
Affiliations
Alejandro Urdiciain
Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain
Elena Erausquin
Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain
María V. Zelaya
Department of Pathology, Hospital Complex of Navarra, 31008 Pamplona, Spain
Idoya Zazpe
Department of Neurosurgery, Hospital Complex of Navarra, 31008 Pamplona, Spain
José L. Lanciego
Neurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain
Bárbara Meléndez
Molecular Pathology Research Unit, Virgen de la Salud Hospital, 45005 Toledo, Spain
Juan A. Rey
IdiPaz Research Unit, La Paz University Hospital, 28046 Madrid, Spain
Miguel A. Idoate
Department of Pathology, University of Navarra Clinic, 31008 Pamplona, Spain
Natalia A. Riobo-Del Galdo
School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
Javier S. Castresana
Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain
Glioblastoma multiforme, the most common type of malignant brain tumor as well as the most aggressive one, lacks an effective therapy. Glioblastoma presents overexpression of mesenchymal markers Snail, Slug, and N-Cadherin and of the autophagic marker p62. Glioblastoma cell lines also present increased autophagy, overexpression of mesenchymal markers, Shh pathway activation, and lack of primary cilia. In this study, we aimed to evaluate the role of HDAC6 in the pathogenesis of glioblastoma, as HDAC6 is the most overexpressed of all HDACs isoforms in this tumor. We treated glioblastoma cell lines with siHDAC6. HDAC6 silencing inhibited proliferation, migration, and clonogenicity of glioblastoma cell lines. They also reversed the mesenchymal phenotype, decreased autophagy, inhibited Shh pathway, and recovered the expression of primary cilia in glioblastoma cell lines. These results demonstrate that HDAC6 might be a good target for glioblastoma treatment.
