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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(More)
Synovial sarcoma (SS) is a malignant soft tissue tumor characterized by its unique t(X;18)(p11;q11) chromosomal translocation leading to the formation of the SS18-SSX fusion gene. The resulting fusion protein product is considered to play as an aberrant transcription factor and transform target cells by perturbing their gene expression program. However, the(More)
In order to display the full metastatic phenotype, the cancer cell must acquire the ability to migrate. In breast cancer, we have previously shown that insulin-like growth factor I (IGF-I) enhances cell motility in the highly metastatic MDA-231BO cell line by activating the type I IGF receptor (IGF1R). This motility response requires activation of IRS-2 and(More)
Synovial sarcoma (SS) is an aggressive soft-tissue malignancy characterized by a unique t(X;18) translocation resulting in expression of SS18-SSX fusion protein. In order to investigate the biological function of this fusion protein and to develop a novel therapeutic option, we examined downregulation of SS18-SSX1 expression by small interfering RNA(More)
Metastasis is responsible for most cancer deaths. Here, we show that Aes (or Grg5) gene functions as an endogenous metastasis suppressor. Expression of Aes was decreased in liver metastases compared with primary colon tumors in both mice and humans. Aes inhibited Notch signaling by converting active Rbpj transcription complexes into repression complexes on(More)
Cell migration is essential for both organogenesis and tumor progression. Bone morphogenetic proteins (BMPs) are reported to be critical for not only bone formation but also tumor invasion. Here, we found that treatment with recombinant human BMP-2 (rhBMP-2) enhanced the haptotactic response of murine osteoblastic MC3T3-E1 and osteosarcoma Dunn cells to(More)
Osteoblast recruitment to the site of future bone formation is essential for skeletal development, bone remodeling and fracture healing. A number of factors associated with bone tissue have been reported to induce directional migration of osteoblasts but the mechanism remains to be clarified. In this study, to explore a major chemotactic factor(s) for(More)
We screened the small molecule compounds that stimulate osteogenesis by themselves or promote bone morphogenetic protein (BMP)-induced bone formation. We found that a specific inhibitor for MAPK/extracellular signal-regulated kinase kinase (MEK)-1, promoted the early osteoblastic differentiation and mineralization of extracellular matrix (ECM) in C2Cl2(More)
We have previously shown that overexpression of LIM kinase1 (LIMK1) resulted in a marked retardation of the internalization of the receptor-mediated endocytic tracer, Texas red-labeled epidermal growth factor (EGF) in low-invasive human breast cancer cell MCF-7. We thereby postulate that LIMK1 signaling plays an important role in the regulation of(More)
To investigate the role of RhoA on the intracellular membrane dynamics of lysosomes in rat hepatoma cells (MM1), we analyzed the localization of lysosomal aspartic proteinase cathepsin D by confocal immunofluorescence microscopy in the dominant active RhoA-transfected cells. Here we show that the transfection of the dominant active form of human small(More)