Abstract
Abstract Cancer metastasis occurs when cells detach from the primary tumor, invade through local tissues, migrate to distant sites, and colonize new tumors. The morphological change within the cell is termed epithelial-mesenchymal transition (EMT), as cells change from their epithelial state and derive more primitive, mesenchymal characteristics. A cellular signaling pathway that stimulates EMT is initiated by hepatocyte growth factor (HGF), which binds and activates the c-Met receptor tyrosine kinase. Activation of HGF signaling induces dramatic changes in cell morphology and behavior. HGF signaling exerts its effect by altering gene transcription and proteome profiles in cells triggered to undergo EMT. The proteomic changes in HGF-induced cell lines is well documented, however changes in lipid expression and their contribution to EMT are poorly understood. Here we develop and employ mass spectrometry-based approaches to analyze lipid expression changes in cells. This method allows for analysis of thousands of lipids in a single sample and the determination of the relative abundance in each lipid. We have found that seventy lipids undergo dramatic regulatory expression changes in MDCK cells undergoing HGF-induced EMT. This effort could provide important clues into the identity of lipid modification or synthesis programs that are required for EMT and, more broadly speaking, for cellular events associated with cancer progression. Understanding their contribution and function could allow for identification of therapeutic targets for intervention in cellular processes required for cancer metastasis. Citation Format: Kristen Alexander, Brendan Coutu, John Prince, Marc Hansen. Lipid expression dynamics in epithelial cells undergoing HGF-induced EMT. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C59.
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