eprintid: 22442
rev_number: 11
eprint_status: archive
userid: 1589
dir: disk0/00/02/24/42
datestamp: 2017-01-04 14:48:58
lastmod: 2024-03-12 17:51:17
status_changed: 2017-01-04 14:48:58
type: article
metadata_visibility: show
creators_name: Frömberg, Anja
creators_name: Rabe, Michael
creators_name: Oppermann, Henry
creators_name: Gaunitz, Frank
creators_name: Aigner, Achim
title: Analysis of cellular and molecular antitumor effects upon inhibition of SATB1 in glioblastoma cells
subjects: 610
divisions: 910500
abstract: Background: The Special AT-rich Sequence Binding Protein 1 (SATB1) regulates the expression of many genes by acting as a global chromatin organizer. While in many tumor entities SATB1 overexpression has been observed and connected to pro-tumorigenic processes, somewhat contradictory evidence exists in brain tumors with regard to SATB1 overexpression in glioblastoma and its association with poorer prognosis and tumor progression. On the functional side, initial data indicate that SATB1 may be involved in several tumor cell-relevant processes.   Methods: For the detailed analysis of the functional relevance and possible therapeutic potential of SATB1 inhibition, we employ transient siRNA-mediated knockdown and comprehensively analyze the cellular and molecular role of SATB1 in glioblastoma.   Results: In various cell lines with different SATB1 expression levels, a SATB1 gene dose-dependent inhibition of anchorage-dependent and –independent proliferation is observed. This is due to cell cycle-inhibitory and pro-apoptotic effects of SATB1 knockdown. Molecular analyses reveal SATB1 knockdown effects on multiple important (proto-) oncogenes, including Myc, Bcl-2, Pim-1, EGFR, β-catenin and Survivin. Molecules involved in cell cycle, EMT and cell adhesion are affected as well. The putative therapeutic relevance of SATB1 inhibition is further supported in an in vivo tumor xenograft mouse model, where the treatment with polymeric nanoparticles containing SATB1-specific siRNAs exerts antitumor effects.   Conclusion: Our results demonstrate that SATB1 may represent a promising target molecule in glioblastoma therapy whose inhibition or knockdown affects multiple crucial pathways.
date: 2017
publisher: BioMed Central; Springer
id_scheme: DOI
ppn_swb: 1655354701
own_urn: urn:nbn:de:bsz:16-heidok-224422
language: eng
bibsort: FROMBERGANANALYSISOF2017
full_text_status: public
publication: BMC Cancer
volume: 17
number: 3
place_of_pub: London; Berlin; Heidelberg
pagerange: 1-11
issn: 1471-2407
citation:   Frömberg, Anja ; Rabe, Michael ; Oppermann, Henry ; Gaunitz, Frank ; Aigner, Achim  (2017) Analysis of cellular and molecular antitumor effects upon inhibition of SATB1 in glioblastoma cells.  BMC Cancer, 17 (3).  pp. 1-11.  ISSN 1471-2407     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/22442/1/12885_2016_Article_3006.pdf