Premium
Role of transforming growth factor‐β1 in recessive dystrophic epidermolysis bullosa squamous cell carcinoma
Author(s) -
Twaroski Kirk,
Chen Weili,
PickettLeonard Michael,
Tolar Jakub
Publication year - 2021
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.14304
Subject(s) - cancer research , mapk/erk pathway , cell , signal transduction , cell culture , transforming growth factor , epithelial–mesenchymal transition , fibroblast , medicine , biology , metastasis , chemistry , cancer , microbiology and biotechnology , genetics
Squamous cell carcinoma (SCC) develops in more than 80% of individuals with the skin blistering disorder recessive dystrophic epidermolysis bullosa (RDEB). In contrast with UV‐induced SCC, RDEB‐SCC results from skin damage and has a high proliferative and metastatic rate with 5‐year survival near zero. Our objective is to determine the mechanisms underlying the increased metastatic tendencies of RDEB‐SCC. RDEB‐SCC cultured cell lines were treated with RDEB and non‐RDEB fibroblast conditioned media and assayed for migration and invasion with and without small molecule inhibitors for TGFβ and other downstream signal transduction pathways. TGFβ1 secreted by RDEB dermal fibroblasts has been found to induce migration and invasion and to increase expression of epithelial‐to‐mesenchymal transition markers in an RDEB‐SCC line. These effects were reversed upon inhibition of TGFβ signalling and its downstream pathways MEK/ERK, P38 kinase and SMAD3. A number of small molecule inhibitors for these pathways are in different phases of various clinical trials and may be applicable to RDEB‐SCC patients. Studying the mechanisms of the extreme form RDEB‐SCC may inform studies of other types of SCC, as well as lead to better therapies for RDEB patients.