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@ARTICLE{Linder:169388,
author = {B. Linder and C. Klein and M. E. Hoffmann and F. Bonn and
I. Dikic and D. Kögel$^*$},
title = {{BAG}3 is a negative regulator of ciliogenesis in
glioblastoma and triple-negative breast cancer cells.},
journal = {Journal of cellular biochemistry},
volume = {123},
number = {1},
issn = {1097-4644},
address = {New York, NY},
publisher = {Wiley-Liss},
reportid = {DKFZ-2021-01462},
pages = {77-90},
year = {2022},
note = {2022 Jan;123(1):77-90},
abstract = {By regulating several hallmarks of cancer, BAG3 exerts
oncogenic functions in a wide variety of malignant diseases
including glioblastoma (GBM) and triple-negative breast
cancer (TNBC). Here we performed global
proteomic/phosphoproteomic analyses of CRISPR/Cas9-mediated
isogenic BAG3 knockouts of the two GBM lines U343 and U251
in comparison to parental controls. Depletion of BAG3 evoked
major effects on proteins involved in ciliogenesis/ciliary
function and the activity of the related kinases
aurora-kinase A and CDK1. Cilia formation was significantly
enhanced in BAG3 KO cells, a finding that could be confirmed
in BAG3-deficient versus -proficient BT-549 TNBC cells, thus
identifying a completely novel function of BAG3 as a
negative regulator of ciliogenesis. Furthermore, we
demonstrate that enhanced ciliogenesis and reduced
expression of SNAI1 and ZEB1, two key transcription factors
regulating epithelial to mesenchymal transition (EMT) are
correlated to decreased cell migration, both in the GBM and
TNBC BAG3 knockout cells. Our data obtained in two different
tumor entities identify suppression of EMT and ciliogenesis
as putative synergizing mechanisms of BAG3-driven tumor
aggressiveness in therapy-resistant cancers.},
keywords = {BAG3 (Other) / cell migration (Other) / epithelial to
mesenchymal transition (Other) / glioblastoma (Other) /
primary cilium (Other) / triple-negative breast cancer
(Other)},
cin = {FM01},
ddc = {540},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34180073},
doi = {10.1002/jcb.30073},
url = {https://inrepo02.dkfz.de/record/169388},
}