4-Hydroxyacetophenone modulates the actomyosin cytoskeleton to reduce metastasis
- 26 August 2020
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 117 (36), 22423-22429
- https://doi.org/10.1073/pnas.2014639117
Abstract
Metastases are the cause of the vast majority of cancer deaths. In the metastatic process, cells migrate to the vasculature, intravasate, extravasate, and establish metastatic colonies. This pattern of spread requires the cancer cells to change shape and to navigate tissue barriers. Approaches that block this mechanical program represent new therapeutic avenues. We show that 4-hydroxyacetophenone (4-HAP) inhibits colon cancer cell adhesion, invasion, and migration in vitro and reduces the metastatic burden in an in vivo model of colon cancer metastasis to the liver. Treatment with 4-HAP activates nonmuscle myosin-2C (NM2C) (MYH14) to alter actin organization, inhibiting the mechanical program of metastasis. We identify NM2C as a specific therapeutic target. Pharmacological control of myosin isoforms is a promising approach to address metastatic disease, one that may be readily combined with other therapeutic strategies.Funding Information
- HHS | NIH | National Institute of General Medical Sciences (GM109863)
- HHS | NIH | National Institute of General Medical Sciences (GM124272)
- HHS | NIH | National Cancer Institute (P30CA014599)
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