Abstract 5136: Sulfiredoxin promotes cell migration through direct interaction with non muscle myosin IIa

Abstract

Abstract Redox homeostasis is frequently dysregulated in cancer cells. In particular, glutathione pathways can be imbalanced and impact cell proliferation and death pathways. S-glutathionylation is the addition of glutathione to basic cysteine residues in certain proteins producing significant changes in their structure/function. Because this post-translational modification is dynamic and reversible, the S-glutathionylation cycle can provide the framework for important cell signaling events in cancer cells. We have shown that sulfiredoxin (Srx) plays a role in deglutathionylation and interacts with proteins such as the phosphatase PTP1B, actin and peroxiredoxin 6 (Prdx 6). Redox regulation of actin modulates cell adhesion and focal contacts. In the present study, we examined the role of Srx in cell migration, invasion and potentially metastasis. Srx was over-expressed by transfection in lung cancer cells (A549). Phalloidin staining showed that Srx over-expression (A549-Srx) led to phenotypic changes in cell adhesion through altered focal adhesion contact points and the cells were more refractory to trypsin release. Relative to wild type, A549-Srx cells showed enhanced migration and invasion in the scratch- and Boyden chamber assays. Proteomic analysis through mass spectrometry demonstrated that Srx interacts with non-muscle myosin IIa (NMIIa) in A549 cells. Reciprocal co-immunoprecipitation of Srx and NMIIa validated this interaction under non-stressed conditions. Either through protein: protein interaction or through redox regulation (or both), Srx appears to be an important mediator of the cell motility and invasive properties of the A549 human lung cancer cell line. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5136.