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@ARTICLE{Even:143038,
author = {I. Even$^*$ and S. Reidenbach$^*$ and T. Schlechter$^*$ and
N. Berns and R. Herold$^*$ and W. Roth$^*$ and D. Krunic$^*$
and V. Riechmann and I. Hofmann$^*$},
title = {{DLIC}1, but not {DLIC}2, is upregulated in colon cancer
and this contributes to proliferative overgrowth and
migratory characteristics of cancer cells.},
journal = {The FEBS journal},
volume = {286},
number = {4},
issn = {1742-464X},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {DKFZ-2019-00657},
pages = {803 - 820},
year = {2019},
note = {DKFZ ZMBH Alliance},
abstract = {Cytoplasmic dynein-1 is a large minus-end-directed
microtubule motor complex involved in membrane trafficking,
organelle positioning, and microtubule organization. The
roles of dynein light intermediate chains (DLICs; DLIC1 and
DLIC2) within the complex are, however, still largely
undefined. In this study, we investigated the possible roles
of DLICs in epithelial homeostasis and colon cancer
development. Mutant clonal analysis of Drosophila Dlic in
the follicular epithelium of Drosophila ovary showed defects
in nuclear positioning, epithelial integrity, and apical
cell polarity. Consistently, knockdown of human DLIC1 and
DLIC2 in colon carcinoma cells resulted in damaged
epithelial organization, disturbed lumen formation, and
impaired apical polarity establishment in three-dimensional
cell culture. Depletion of DLIC1 and DLIC2 led to reduced
proliferation, enhanced apoptosis rates, disrupted mitotic
spindle assembly, and induction of G2/M arrest in cell cycle
progression. Moreover, reduced levels of DLIC1 in contrast
to DLIC2 impaired the migratory ability. On the other hand,
immunohistochemical examination of human colorectal tissue
samples and further colorectal cancer dataset analysis
showed a significant upregulation for DLIC1 in tumors,
whereas DLIC2 expression was unchanged. In addition, the
overexpression of DLIC1 caused increased proliferation,
decreased apoptosis and enhanced migration, whereas DLIC2
overexpression did not result in any significant changes.
Together, these results indicate that DLIC1 and DLIC2
contribute to the establishment and maintenance of
epithelial homeostasis. Furthermore, these findings present
the first evidence that DLIC1 and DLIC2 have distinct roles
in colon cancer development and that DLIC1 may contribute to
proliferative overgrowth and migratory characteristics.},
cin = {A190 / G150 / W210},
ddc = {610},
cid = {I:(DE-He78)A190-20160331 / I:(DE-He78)G150-20160331 /
I:(DE-He78)W210-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30657258},
doi = {10.1111/febs.14755},
url = {https://inrepo02.dkfz.de/record/143038},
}