Complex and variable regulation of ΔNp63 and TAp63 by TGFβ has implications for the dynamics of squamous cell epithelial to mesenchymal transition

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F24%3A00079755" target="_blank" >RIV/00209805:_____/24:00079755 - isvavai.cz</a>

Result on the web

<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10973453/" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10973453/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-024-57895-1" target="_blank" >10.1038/s41598-024-57895-1</a>

Result language

angličtina

Original language name

Complex and variable regulation of ΔNp63 and TAp63 by TGFβ has implications for the dynamics of squamous cell epithelial to mesenchymal transition

Original language description

TGFβ has roles in inflammation, wound healing, epithelial to mesenchymal transition (EMT), and cancer stem cell states, and acts as a tumor suppressor gene for squamous cell carcinoma (SCC). SCCs are also characterized by high levels of ΔNp63, which induces epithelial cell phenotypes and maintains squamous stem cells. Previous studies indicate a complex interplay between ΔNp63 and TGFβ signaling, with contradictory effects reported. We investigated the effects of TGFβ on p63 isoform proteins and mRNAs in non-malignant squamous and SCC cells, and the role of either canonical or non-canonical TGFβ signaling pathways. TGFβ selectively increased ΔNp63 protein levels in non-malignant keratinocytes in association with SMAD3 activation and was prevented by TGFβ receptor inhibition, indicating activation of canonical TGFβ pathway signaling. TP63 isoform mRNAs showed discordance from protein levels, with an initial increase in both TAP63 and ΔNP63 mRNAs followed by a decrease at later times. These data demonstrate complex and heterogeneous effects of TGFβ in squamous cells that depend on the extent of canonical TGFβ pathway aberrations. The interplay between TGFβ and p63 is likely to influence the magnitude of EMT states in SCC, with clinical implications for tumor progression and response to therapy.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/GA23-05951S" target="_blank" >GA23-05951S: Mechanisms and Effects of Inverse TAp63 and ΔNp63 Regulation</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific reports

ISSN

2045-2322

e-ISSN

2045-2322

Volume of the periodical

14

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

7304

UT code for WoS article

001196356400039

EID of the result in the Scopus database

2-s2.0-85188932423