Retinoic acid receptor β modulates mechanosensing and invasion in pancreatic cancer cells via myosin light chain 2
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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 in pancreatic cancer cells. As a key regulatory component of the contractile actomyosin machinery, 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. This work highlights the potential of retinoids to target the mechanical drivers of pancreatic cancer.
Date Issued
2023-05-02
Date Acceptance
2023-04-13
Citation
Oncogenesis, 2023, 12, pp.1-11
ISSN
2157-9024
Publisher
Nature Publishing Group
Start Page
1
End Page
11
Journal / Book Title
Oncogenesis
Volume
12
Replaces
10044/1/103950
Copyright Statement
© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37130839
PII: 10.1038/s41389-023-00467-1
Publication Status
Published
Coverage Spatial
United States
Article Number
23
Date Publish Online
2023-05-02