期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 36, 页码 22423-22429出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2014639117
关键词
colorectal cancer; nonmuscle myosin 2C; 4-hydroxyacetophenone; ex vivo motility; metastasis
资金
- University of Chicago Research Computing Center
- NIH [R01 GM109863, R01 GM124272]
- Cancer Center Support Grant [P30CA014599]
- Ludwig Foundation
- Johns Hopkins Discovery Grant
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.
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