Year-end Sale % OFF 
Abstract
BackgroundThe local invasion of tumor cells into the surrounding tissue is the first and most critical step of the metastatic cascade. Cells can invade either collectively, or individually. Individual cancer cell invasion can occur in the mesenchymal or amoeboid mode, which are mutually interchangeable. This plasticity of individual cancer cell invasiveness may represent an escape mechanism for invading cancer cells from anti-metastatic treatment.MethodsTo identify new signaling proteins involved in the plasticity of cancer cell invasiveness, we performed proteomic analysis of the amoeboid to mesenchymal transition with A375m2 melanoma cells in a 3D Matrigel matrix.ResultsIn this screen we identified PKCα as an important protein for the maintenance of amoeboid morphology. We found that the activation of PKCα resulted in the mesenchymal-amoeboid transition of mesenchymal K2 and MDA-MB-231 cell lines. Consistently, PKCα inhibition led to the amoeboid-mesenchymal transition of amoeboid A375m2 cells. Next, we showed that PKCα inhibition resulted in a considerable decrease in the invading abilities of all analyzed cancer cell lines.ConclusionsOur results suggest that PKCα is an important protein for maintenance of the amoeboid morphology of cancer cells, and that downregulation of PKCα results in the amoeboid to mesenchymal transition. Our data also suggest that PKCα is important for both mesenchymal and amoeboid invasiveness, making it an attractive target for anti-metastatic therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1347-1) contains supplementary material, which is available to authorized users.
Highlights
The local invasion of tumor cells into the surrounding tissue is the first and most critical step of the metastatic cascade
Protein microarray analysis reveals the down-regulation of PKCα phosphorylation in highly metastatic amoeboid A375m2 melanoma cells after amoeboid-mesenchymal transition (AMT) To identify new proteins involved in amoeboid invasiveness and the AMT, we analyzed proteomic profiles of cells before and after AMT
We used amoeboid melanoma A375m2 cells that were cultivated in 3D Matrigel and either induced AMT with the ROCK kinase inhibitor Y-27632 or left the cells untreated
Summary
The local invasion of tumor cells into the surrounding tissue is the first and most critical step of the metastatic cascade. Cells can invade either collectively, or individually. Individual cancer cell invasion can occur in the mesenchymal or amoeboid mode, which are mutually interchangeable. This plasticity of individual cancer cell invasiveness may represent an escape mechanism for invading cancer cells from anti-metastatic treatment. The local invasion of tumor cells into the surrounding tissue is the first and most critical step of the metastatic cascade, and importantly, it determines the metastatic potential of many tumor cell types. Cells can invade through tissue and the extracellular matrix (ECM) either collectively, or individually. Amoeboid cancer cell invasion is mediated by the contractions of cortical actin, which is regulated by the Rho/ROCK signaling pathway
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
