Transforming growth factor-β (TGF-β) signaling is essential for cell growth and
differentiation and is often dysregulated in human cancers. Here, we combine genetic
engineering of a human organotypic 3D skin model using N/TERT-1 immortalized
primary keratinocytes with global quantitative proteomics and phosphoproteomics to
dissect the importance of essential components of the TGF-β signaling pathway. We
first acquire deep proteomes of the N/TERT-1 cell line and human skin epidermis,
demonstrating high biological relevance of the skin model. By knocking out SMAD4,
our results show that loss of Smad4-dependent TGF-β signaling delays differentiation
of human skin through the regulation of cell cycle components and extracellular
matrix proteins. In contrast, the combined loss of Smad4-dependent and -independent
TGF-β signaling through the deletion of the type II TGF-β receptor causes activation
of p38 and ERK signaling and induces invasive tissue growth. The study provides a
framework for exploration of TGF-β signaling pathways in human epithelial tissue
homeostasis and transformation using genetic engineering, 3D tissue models, and
high-throughput quantitative proteomics and phosphoproteomics.

LB054 - Loss of transforming growth factor-β receptor II signaling induce invasive growth in human skin 3D-models

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.