LIM kinase 1 is essential for the invasive growth of prostate epithelial cells: implications in prostate cancer.
Mammalian LIM kinase 1 (LIMK1) is involved in reorganization of actin cytoskeleton through inactivating phosphorylation of the ADF family protein cofilin, which depolymerizes actin filaments. Maintenance of the actin dynamics in an ordered fashion is essential for stabilization of cell shape or promotion of cell motility depending on the cell type. These are the two key phenomena that may become altered during acquisition of the metastatic phenotype by cancer cells. Here we show that LIMK1 is overexpressed in prostate tumors and in prostate cancer cell lines, that the concentration of phosphorylated cofilin is higher in metastatic prostate cancer cells, and that a partial reduction of LIMK1 altered cell proliferation by arresting cells at G2/M, changed cell shape, and abolished the invasiveness of metastatic prostate cancer cells. We also show that the ectopic expression of LIMK1 promotes acquisition of invasive phenotype by the benign prostate epithelial cells. Our data provide evidence of a novel role of LIMK1 in regulating cell division and invasive property of prostate cancer cells and indicate that the effect is not mediated by phosphorylation of cofilin. Our study correlates with the recent observations showing a metastasis-associated chromosomal gain on 7q11.2 in prostate cancer, suggesting a possible gain in LIMK1 DNA (7q11.23).
Davila
Monica
M
Department of Molecular Biology and Microbiology University of Central Florida, Orlando, Florida 32826, USA.
Frost
Andra R
AR
Grizzle
William E
WE
Chakrabarti
Ratna
R
D051339:Actin Depolymerizing Factors; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D002469:Cell Separation; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D016195:G2 Phase; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D054461:Lim Kinases; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008938:Mitosis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010641:Phenotype; D010766:Phosphorylation; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D013936:Thymidine / Q000737:chemistry; D013997:Time Factors; D014162:Transfection
D051339:Actin Depolymerizing Factors; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D011994:Recombinant Proteins; D004247:DNA; D011494:Protein Kinases; C515892:LIMK1 protein, human; D054461:Lim Kinases; D017346:Protein Serine-Threonine Kinases; D013936:Thymidine