% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Kirschberg:176895,
author = {M. Kirschberg and A. S. Syed and H. G. Dönmez and S.
Heuser and A. Wilbrand-Hennes and A. Alonso$^*$ and M.
Hufbauer and B. Akgül},
title = {{N}ovel {I}nsights {I}nto {C}ellular {C}hanges in
{HPV}8-{E}7 {P}ositive {K}eratinocytes: {A} {T}ranscriptomic
and {P}roteomic {A}nalysis.},
journal = {Frontiers in microbiology},
volume = {12},
issn = {1664-302X},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2021-02137},
pages = {672201},
year = {2021},
abstract = {Human papillomavirus type 8 (HPV8) is associated with the
development of non-melanoma skin cancer. In the past we
already delved into the mechanisms involved in keratinocyte
invasion, showing that the viral E7 oncoprotein is a key
player that drives invasion of basal keratinocytes
controlled by the extracellular protein fibronectin. To
unravel further downstream effects in E7 expressing
keratinocytes we now aimed at characterizing gene and
protein/phosphoprotein alterations to narrow down on key
cellular targets of HPV8-E7. We now show that gene
expression of GADD34 and GDF15 are strongly activated in the
presence of E7 in primary human keratinocytes. Further
analyses of fibronectin-associated factors led to the
identification of the Src kinase family members Fyn and Lyn
being aberrantly activated in the presence of HPV8-E7.
Phospho-proteomics further revealed that E7 not only targets
cell polarity and cytoskeletal organization, but also
deregulates the phosphorylation status of nuclear proteins
involved in DNA damage repair and replication. Many of these
differentially phosphorylated proteins turned out to be
targets of Fyn and Lyn. Taken together, by using unbiased
experimental approaches we have now arrived at a deeper
understanding on how fibronectin may affect the signaling
cascades in HPV8 positive keratinocytes, which may be key
for skin tumorigenesis and that may also aid in the
development of novel therapeutic approaches for
betaHPV-mediated cancers.},
keywords = {E7 oncoprotein (Other) / betapapillomavirus (Other) /
fibronectin (Other) / keratinocyte invasion (Other) / skin
cancer (Other)},
cin = {F050},
ddc = {570},
cid = {I:(DE-He78)F050-20160331},
pnm = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
pid = {G:(DE-HGF)POF4-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34552568},
pmc = {pmc:PMC8450583},
doi = {10.3389/fmicb.2021.672201},
url = {https://inrepo02.dkfz.de/record/176895},
}