Cancer Research
Research Toward a Cure
Tissue Invasion and Metastasis
Tissue Invasion and Metastasis—More examples from the literature:
Invasion and metastasis allow cancer cells to break free of the primary tumor and spread to new locations. The process begins with local invasion and intravasation into the circulatory system. After traveling to distant tissues, cancer cells must adapt to a new tissue microenvironment and develop from micrometastasis to a macroscopic tumor.
Changes in extracellular matrix (ECM) interactions and extracellular proteases lead to increased migration and invasion. Examples include altered expression of cell-cell or cell-ECM adhesion molecules, and triggering of the epithelial-mesenchymal transition (EMT).
Tyrosine Phosphorylation of Cortactin Inhibits Interaction with Focal Adhesion Kinase (FAK)
Figure 1. Acetylation and tyrosine phosphorylation of transfected cortactin. Transfected cells were treated with Trichostatin A (TSA), a deacetylase inhibitor. Cell lysates were subjected to parallel IP experiments with myc mAb and a generic pTyr mAb. Left: Acetyl-cortactin (green) and myc (red) were detected (overlapping signals shown in yellow). Center: After stripping, pY466 cortactin (green) and myc (red) were detected (overlapping signals are yellow). Right: Quantification showed a statistically significant inverse relationship between acetylation and tyrosine phosphorylation. Fluorescent Westerns were imaged with Odyssey® CLx. a.u.: arbitrary units. *, p,0.05; **, p,0.01. doi:10.1371/journal.pone.0033662.g003
Cortactin is an oncoprotein that affects actin cytoskeletal dynamics, including cell adhesion and spreading. This Src kinase substrate is regulated by both phosphorylation and acetylation, but the function of tyrosine phosphorylation is not understood. Very low levels of tyrosine phosphorylation have made studies difficult and unreliable.
- Two-color quantitative Western blotting, pulldown assays, and fluorescent microscopy were used to analyze cortactin phosphorylation and acetylation.
- Acetylation and phosphorylation of cortactin were mutually exclusive. Phosphorylation of cortactin inhibited cell spreading and adhesion.
- Tyrosine phosphorylation of cortactin prevented interaction of its SH3 domain with focal adhesion kinase (FAK).
E Meiler, E Nieto-Pelegrin, N. Martinez-Quiles Cortactin tyrosine phosphorylation promotes its deacetylation and inhibits cell spreading. PLoS ONE 7(3): e33662. doi:10.1371/journal.pone.0033662 (2012).
