PT  - JOURNAL ARTICLE
AU  - Matellan, Carlos
AU  - Lachowski, Dariusz
AU  - Cortes, Ernesto
AU  - Thorpe, Stephen
AU  - del Río Hernández, Armando E.
TI  - Retinoid acid receptor β mechanically regulates the activity of pancreatic cancer cells
AID  - 10.1101/2022.08.10.503236
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.08.10.503236
4099  - http://biorxiv.org/content/early/2022/08/13/2022.08.10.503236.short
4100  - http://biorxiv.org/content/early/2022/08/13/2022.08.10.503236.full
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.