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@ARTICLE{Weber:148382,
author = {S. Weber$^*$ and S. E. Koschade$^*$ and C. M. Hoffmann$^*$
and T. D. Dubash$^*$ and K. Giessler$^*$ and S. Dieter$^*$
and F. Herbst$^*$ and H. Glimm$^*$ and C. Ball$^*$},
title = {{T}he notch target gene {HEYL} modulates metastasis forming
capacity of colorectal cancer patient-derived spheroid cells
in vivo.},
journal = {BMC cancer},
volume = {19},
number = {1},
issn = {1471-2407},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2019-02938},
pages = {1181},
year = {2019},
note = {EA:L501LA:L301},
abstract = {While colorectal cancer (CRC) patients with localized
disease have a favorable prognosis, the five-year-survival
rate in patients with distant spread is still below $15\%.$
Hence, a detailed understanding of the mechanisms regulating
metastasis formation is essential to develop therapeutic
strategies targeting metastasized CRC. The notch pathway has
been shown to be involved in the metastatic spread of
various tumor entities; however, the impact of its target
gene HEYL remains unclear so far.In this study, we
functionally assessed the association between high HEYL
expression and metastasis formation in human CRC. Therefore,
we lentivirally overexpressed HEYL in two human
patient-derived CRC cultures differing in their spontaneous
metastasizing capacity and analyzed metastasis formation as
well as tumor cell dissemination into the bone marrow after
xenotransplantation into NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ
(NSG) mice.HEYL overexpression decreased tumor cell
dissemination and the absolute numbers of formed metastases
in a sub-renal capsular spontaneous metastasis formation
model, addressing all steps of the metastatic cascade. In
contrast, metastatic capacity was not decreased following
intrasplenic xenotransplantation where the cells are placed
directly into the blood circulation.These results suggest
that HEYL negatively regulates metastasis formation in vivo
presumably by inhibiting intravasation of
metastasis-initiating cells.},
cin = {L501 / L301 / B280},
ddc = {610},
cid = {I:(DE-He78)L501-20160331 / I:(DE-He78)L301-20160331 /
I:(DE-He78)B280-20160331},
pnm = {899 - ohne Topic (POF3-899)},
pid = {G:(DE-HGF)POF3-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31796022},
doi = {10.1186/s12885-019-6396-4},
url = {https://inrepo02.dkfz.de/record/148382},
}