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2014-2015: Proposed research project 06

Roles of membrane lipids in the epithelial-tube morphogenesis
Leader : Junichi Ikenouchi
Research progress

The epithelium-mesenchyme transition (EMT) has attracted increasing interest from both developmental cell biologists and cancer researchers. EMT occurs in various steps in normal development, including mesoderm and neural-crest formation. Furthermore, the process of acquisition of an invasive phenotype by tumors of epithelial origin can be regarded as a pathological version of EMT.

Snail is a transcription repressor that plays a central role in the EMT. We and others have reported that expression of epithelial-cell specific cell adhesion molecules such as E-cadherin, claudins, occludin and tricellulin was down-regulated by Snail (Ikenouchi etl al. 2003 JCS; Ikenouchi et al. 2005 JCB; Ikenouchi et al. 2010 PNAS). Considering that these membrane proteins are embedded in the plasma membrane, I hypothesized that epithelial-cell specific lipid species could exist and function co-operatively with these membrane proteins.

In my research project, I examined this hypothesis. I compared the lipid profile of mouse cultured EpH4 epithelial cell and that of transformed EpH4 cell by Snail (EpH4-Snail cells). The plasma membranes of these cells were isolated by using colloidal silica particles and the extracted lipids were subjected to mass spectrometric analysis using the electrospray ionization-MS/MS system. So far, I identified several epithelial-cell specific lipid species. I also confirmed that these epithelial-cell specific lipid species were decreased in the invasive cancers. My group is now trying to clarify the physiological roles of such lipid species in the establishment of epithelial polarity and in the formation of cell-cell adhesion.