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@ARTICLE{Adam:126010,
author = {M. G. Adam$^*$ and S. Matt and S. Christian and H.
Hess-Stumpp and A. Haegebarth and T. Hofmann$^*$ and C.
Algire},
title = {{SIAH} ubiquitin ligases regulate breast cancer cell
migration and invasion independent of the oxygen status.},
journal = {Cell cycle},
volume = {14},
number = {23},
issn = {1551-4005},
address = {Georgetown, Tex.},
publisher = {Landes Bioscience},
reportid = {DKFZ-2017-02125},
pages = {3734 - 3747},
year = {2015},
abstract = {Seven-in-absentia homolog (SIAH) proteins are evolutionary
conserved RING type E3 ubiquitin ligases responsible for the
degradation of key molecules regulating DNA damage response,
hypoxic adaptation, apoptosis, angiogenesis, and cell
proliferation. Many studies suggest a tumorigenic role for
SIAH2. In breast cancer patients SIAH2 expression levels
correlate with cancer aggressiveness and overall patient
survival. In addition, SIAH inhibition reduced metastasis in
melanoma. The role of SIAH1 in breast cancer is still
ambiguous; both tumorigenic and tumor suppressive functions
have been reported. Other studies categorized SIAH ligases
as either pro- or antimigratory, while the significance for
metastasis is largely unknown. Here, we re-evaluated the
effects of SIAH1 and SIAH2 depletion in breast cancer cell
lines, focusing on migration and invasion. We successfully
knocked down SIAH1 and SIAH2 in several breast cancer cell
lines. In luminal type MCF7 cells, this led to stabilization
of the SIAH substrate Prolyl Hydroxylase Domain protein 3
(PHD3) and reduced Hypoxia-Inducible Factor 1α (HIF1α)
protein levels. Both the knockdown of SIAH1 or SIAH2 led to
increased apoptosis and reduced proliferation, with
comparable effects. These results point to a tumor promoting
role for SIAH1 in breast cancer similar to SIAH2. In
addition, depletion of SIAH1 or SIAH2 also led to decreased
cell migration and invasion in breast cancer cells. SIAH
knockdown also controlled microtubule dynamics by markedly
decreasing the protein levels of stathmin, most likely via
p27(Kip1). Collectively, these results suggest that both
SIAH ligases promote a migratory cancer cell phenotype and
could contribute to metastasis in breast cancer.},
keywords = {CDKN1B protein, human (NLM Chemicals) / Nuclear Proteins
(NLM Chemicals) / Stathmin (NLM Chemicals) /
Cyclin-Dependent Kinase Inhibitor p27 (NLM Chemicals) /
Ubiquitin-Protein Ligases (NLM Chemicals) / seven in
absentia proteins (NLM Chemicals)},
cin = {A210},
ddc = {570},
cid = {I:(DE-He78)A210-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26654769},
pmc = {pmc:PMC4825722},
doi = {10.1080/15384101.2015.1104441},
url = {https://inrepo02.dkfz.de/record/126010},
}