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@ARTICLE{Hasche:291069,
author = {D. Hasche$^*$ and M. Hufbauer and I. Braspenning-Wesch$^*$
and S. Stephan$^*$ and S. Silling and G. Schmidt$^*$ and S.
Krieg$^*$ and A. Kreuter and B. Akgül},
title = {{C}ytokeratin-17 expression is commonly observed in
keratinocytic skin tumours and controls tissue homeostasis
impacting {HPV} protein expression.},
journal = {British journal of dermatology},
volume = {191},
number = {6},
issn = {0366-2845},
address = {Oxford},
publisher = {Oxford University Press},
reportid = {DKFZ-2024-01289},
pages = {949-963},
year = {2024},
note = {#EA:F030# / 2024 Nov 18;191(6):949-963},
abstract = {The structured expression of several keratins in the skin
is associated with differentiation status of the epidermal
layers, whereas others are upregulated only during wound
healing, in skin disorders and in cancers. One of these
stress keratins, K17, is correlated with poor prognosis in
various cancer types and its loss has been shown to
decelerate tumour growth. K17 expression can also be
detected in cutaneous squamous cell carcinomas (SCCs), where
UV-irradiation and infection with cutaneous human
papillomaviruses (HPVs) are important co-factors. It was
previously reported that K17 is upregulated in
papillomavirus (PV)-induced benign skin lesions in mice and
induces an immunological status that is beneficial for
tumour growth.In order to investigate whether K17
upregulation is induced by PVs, we analysed K17 levels in
skin tumour specimens of different animal models and
humans.Various immunofluorescence stainings were performed
to identify K17 expression as well as levels of E-Cadherin,
vimentin and CD271. Tissues were further analysed by PCRs,
qPCRs and ELISA to control for PV activity. K17knockdown
cells were generated and effects on viral life cycle were
investigated by infection assays, qPCR and Western
blotting.We could show that K17 is commonly expressed in
skin tumours and that its presence is not directly linked to
viral oncoprotein expression. Rather, K17 expression seems
to be a marker of epithelial differentiation and its absence
in tumour tissue is associated with an
epithelial-to-mesenchymal transition. We further showed that
the absence of K17 in skin tumours increases markers of
cancer stem-like cells and negatively affects viral protein
synthesis.Collectively, our data indicate that K17
expression is a common feature in skin tumourigenesis. While
it is not primarily targeted by PV oncoproteins, our in vivo
and in vitro data suggest that it is an important regulator
of epithelial differentiation and thus may play a role in
controlling viral protein synthesis.},
cin = {F030 / W210 / F190},
ddc = {610},
cid = {I:(DE-He78)F030-20160331 / I:(DE-He78)W210-20160331 /
I:(DE-He78)F190-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38878280},
doi = {10.1093/bjd/ljae255},
url = {https://inrepo02.dkfz.de/record/291069},
}