Up-regulation of Rho/ROCK signaling in sarcoma cells drives invasion and increased generation of protrusive forces
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18819929
DOI
10.1158/1541-7786.mcr-07-2174
PII: 6/9/1410
Knihovny.cz E-resources
- MeSH
- Actins metabolism MeSH
- Cell Adhesion physiology MeSH
- Protein Array Analysis MeSH
- Cytoskeleton metabolism pathology MeSH
- Actin Depolymerizing Factors metabolism MeSH
- Microscopy, Fluorescence MeSH
- Phosphorylation MeSH
- Neoplasm Invasiveness MeSH
- rho-Associated Kinases genetics metabolism MeSH
- Collagen metabolism MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Myosin Light Chains metabolism MeSH
- Lim Kinases genetics metabolism MeSH
- Magnetics MeSH
- Matrix Metalloproteinase 2 metabolism MeSH
- Mesenchymal Stem Cells metabolism pathology MeSH
- Cell Movement physiology MeSH
- rho GTP-Binding Proteins genetics metabolism MeSH
- Sarcoma metabolism pathology MeSH
- Up-Regulation MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Actins MeSH
- Actin Depolymerizing Factors MeSH
- rho-Associated Kinases MeSH
- Collagen MeSH
- Myosin Light Chains MeSH
- Lim Kinases MeSH
- Limk1 protein, rat MeSH Browser
- Matrix Metalloproteinase 2 MeSH
- myosin light chain I MeSH Browser
- rho GTP-Binding Proteins MeSH
Tumor cell invasion is the most critical step of metastasis. Determination of the mode of invasion within the particular tumor is critical for effective cancer treatment. Protease-independent amoeboid mode of invasion has been described in carcinoma cells and more recently in sarcoma cells on treatment with protease inhibitors. To analyze invasive behavior, we compared highly metastatic sarcoma cells with parental nonmetastatic cells. The metastatic cells exhibited a functional up-regulation of Rho/ROCK signaling and, similarly to carcinoma cells, an amoeboid mode of invasion. Using confocal and traction force microscopy, we showed that an up-regulation of Rho/ROCK signaling leads to increased cytoskeletal dynamics, myosin light chain localization, and increased tractions at the leading edge of the cells and that all of these contributed to increased cell invasiveness in a three-dimensional collagen matrix. We conclude that cells of mesenchymal origin can use the amoeboid nonmesenchymal mode of invasion as their primary invading mechanism and show the dependence of ROCK-mediated amoeboid mode of invasion on the increased capacity of cells to generate force.
References provided by Crossref.org
Cytoplasmic Tail of MT1-MMP: A Hub of MT1-MMP Regulation and Function
Complex Interplay of Genes Underlies Invasiveness in Fibrosarcoma Progression Model
The role of focal adhesion anchoring domains of CAS in mechanotransduction
Cell polarity signaling in the plasticity of cancer cell invasiveness
PKCα promotes the mesenchymal to amoeboid transition and increases cancer cell invasiveness
Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling
The transcription factor EGR1 regulates metastatic potential of v-src transformed sarcoma cells
The role of the tissue microenvironment in the regulation of cancer cell motility and invasion
The molecular mechanisms of transition between mesenchymal and amoeboid invasiveness in tumor cells
