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@ARTICLE{Lei:305515,
author = {K. C. Lei$^*$ and N. Kolar Srinivas$^*$ and M. Chandra$^*$
and V. Serobyan$^*$ and S. Ugurel and D. Hoffmann and T.
Kervarrec and W.-O. Lui and J. Becker$^*$},
title = {{H}igh-resolution spatial transcriptomics uncover
epidermal-dermal divergences in {M}erkel cell carcinoma:
spatial context reshapes the gene expression landscape.},
journal = {Oncogene},
volume = {nn},
issn = {0950-9232},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2025-02199},
pages = {nn},
year = {2025},
note = {epub},
abstract = {Merkel cell carcinoma (MCC) is an aggressive skin cancer
with neuroendocrine differentiation marked by high cellular
plasticity, often manifesting as rapid therapy resistance.
Although the cell-of-origin is presumed to be epithelial,
epidermal localization of MCC is rarely observed, largely
because in situ MCC is typically an incidental finding.
Nevertheless, a subset of MCC tumors exhibits
epidermotropism, wherein tumor cells are present in the
epidermis. The behavior of cancer cells is profoundly
influenced by the tumor microenvironment and interactions
with neighboring cells. Notably, the normal counterparts of
the cancer's cell-of-origin have been shown to attenuate
tumor aggressiveness. Thus, epidermotropic MCC presents a
unique opportunity to explore the potential role of
epidermal microenvironment in modulating tumor cell
behavior. While the epidermotropic tumor nests share
histological resemblance with their dermal counterparts,
their transcriptomic profiles remain unexplored. Here, we
employed high-definition spatial and single-cell
transcriptomics to dissect the gene expression profiles of
epidermotropic MCC cells, comparing them to MCC cells in the
tumor core and those adjacent to blood vessels. Notably,
epidermotropic MCC cells exhibit a transcriptomic signature
reminiscent of cutaneous squamous cell carcinoma,
characterized by upregulation of genes encoding keratins,
S100A proteins, as well as calmodulin-like proteins 3 and 5.
Mechanistically, this keratinocytic differentiation is
associated with enhanced p63 activity, leading to the
upregulation of PERP. Collectively, our study demonstrates
that MCC cells can adopt a keratinocytic differentiation
program in response to microenvironmental cues, underscoring
the remarkable phenotypic plasticity of this malignancy and
the importance of the microenvironment for tumor cell
characteristics.},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41131107},
doi = {10.1038/s41388-025-03608-5},
url = {https://inrepo02.dkfz.de/record/305515},
}