A role for LIM kinase in cancer invasion
Details
Publication Year 2003-06-10,Volume 100,Issue #12,Page 7247-7252
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type
Journal Article
Abstract
In this study, we show that LIM kinase 1 (LIMK1), a critical regulator of actin dynamics, plays a regulatory role in tumor cell invasion. We found that the level and activity of endogenous LIMK1 is increased in invasive breast and prostate cancer cell lines in comparison with less invasive cells. Overexpression of LIMK1 in MCF-7 and in MDA-MB-231 human breast cancer cell lines increased their motility, whereas the specific ROCK and Rho inhibitors Y-27632 and C3, respectively, attenuated this effect. In addition, inhibition of LIMK1 activity in the MDA-MB-231 cells by expression of dominant-negative LIMK1 resulted in decreased motility and formation of osteolytic bone lesions in an animal model of tumor invasion. This study shows an important role for LIMK1 signaling in invasion of cancer, demonstrating its potential as a therapeutic molecular target to decrease metastasis.
Publisher
NATL ACAD SCIENCES
Keywords
RHO-ASSOCIATED KINASE; HORMONE-RELATED PROTEIN; BREAST-CANCER; TUMOR-CELLS; BONE METASTASIS; BISPHOSPHONATE IBANDRONATE; SERINE/THREONINE KINASE; COFILIN PHOSPHORYLATION; FOCAL ADHESIONS; STRESS FIBERS
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2003-06-10 12:00:00
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