A role for LIM kinase in cancer invasion.
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.
Yoshioka
Kiyoko
K
Department of Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-2 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
Foletta
Victoria
V
Bernard
Ora
O
Itoh
Kazuyuki
K
D000818:Animals; D001859:Bone Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D054461:Lim Kinases; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009368:Neoplasm Transplantation; D010014:Osteolysis / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C515892:LIMK1 protein, human; D054461:Lim Kinases; C515893:Limk1 protein, mouse