RT Journal Article
SR Electronic
T1 Retinoid acid receptor β mechanically regulates the activity of pancreatic cancer cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.08.10.503236
DO 10.1101/2022.08.10.503236
A1 Matellan, Carlos
A1 Lachowski, Dariusz
A1 Cortes, Ernesto
A1 Thorpe, Stephen
A1 del Río Hernández, Armando E.
YR 2022
UL http://biorxiv.org/content/early/2022/08/13/2022.08.10.503236.abstract
AB Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, characterised by stromal remodelling, elevated matrix stiffness and high metastatic rate. Retinoids, compounds derived from vitamin A, have a history of clinical use in cancer for their anti-proliferative and differentiation effects, and more recently have been explored as anti-stromal therapies in PDAC for their ability to induce mechanical quiescence in cancer associated fibroblasts. Here we demonstrate that retinoic acid receptor β (RAR-β) transcriptionally represses myosin light chain 2 (MLC-2) expression, a key regulatory component of the contractile actomyosin machinery. In turn, MLC-2 downregulation results in decreased cytoskeletal stiffness and traction force generation, impaired response to mechanical stimuli via mechanosensing and reduced ability to invade through the basement membrane.Competing Interest StatementThe authors have declared no competing interest.