Abstract
AbstractPancreatic 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.
Publisher
Cold Spring Harbor Laboratory
Reference75 articles.
1. Pancreatic Ductal Adenocarcinoma: Current and Evolving Therapies;International journal of molecular sciences,2017
2. Cancer Research UK. Pancreatic cancer statistics. [cited 2019 October 2019]; Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer.
3. Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors;World journal of oncology,2019
4. Mechanotransduction in tumor progression: The dark side of the force
5. Quantitative analysis of 3D extracellular matrix remodelling by pancreatic stellate cells