Abstract 4054: Elongation factor-2 kinase (eEF-2K) promotes cell invasion and epithelial mesenchymal transition through regulation of TG2-mediated signaling in human pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) accounts for the majority of pancreatic cancer (PaCa) cases and is currently uncurable with poor prognosis/survival rates (∼4% 5-year survival). The extensive local tumor invasion, early metastasis/systemic dissemination and resistance to existing cancer therapies are the major characteristics of PaCa and the impediment to effective cure of this disease. Although PaCa has a well-defined spectrum of highly oncogenic lesions (e.g, mutations in K-RAS, p53, p16ink4a, and SMAD4/DPC4), effective therapies have not yet been developed. Therefore, novel molecular targets-based therapeutic strategies are urgently needed. Recently, we discovered that eukaryotic elongation factor-2 kinase (eEF-2K) is dramatically up-regulated in different PaCa cells, promoting their survival, and that targeted-silencing of eEF-2K led to significant cell death (Ashour et al, 2013). However, the role of eEF-2K in the pathways regulating invasion/metastasis and drug-resistance remains largely unknown. Here, we show that siRNA-mediated knockdown of eEF-2K markedly inhibits the invasion of PANC-1and MIAPaCa-2 cells. Furthermore, rottlerin, which we found to down-regulate eEF-2K expression, also significantly reduced the invasion of both cell lines. We later investigated the involvement of tissue transglutaminase (TG2), a multifunctional enzyme implicated in regulation of cell survival, migration and invasion. We found that eEF-2K regulates TG2 at the transcription lev...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Biology Source Type: research