anomalous features of emt during keratinocyte transformationemt在角化细胞的异常特征转换.pdfVIP

Anomalous Features of EMT during Keratinocyte Transformation 1 2 1 2 1 Tamar Geiger , Helena Sabanay , Nataly Kravchenko-Balasha , Benjamin Geiger , Alexander Levitzki * 1 Department of Biological Chemistry, Institute of Life Science, The Hebrew University, Jerusalem, Israel, 2 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel Abstract During the evolution of epithelial cancers, cells often lose their characteristic features and acquire a mesenchymal phenotype, in a process known as epithelial-mesenchymal transition (EMT). In the present study we followed early stages of keratinocyte transformation by HPV16, and observed diverse cellular changes, associated with EMT. We compared primary keratinocytes with early and late passages of HF1 cells, a cell line of HPV16-transformed keratinocytes. We have previously shown that during the progression from the normal cells to early HF1 cells, immortalization is acquired, while in the progression to late HF1, cells become anchorage independent. We show here that during the transition from the normal state to late HF1 cells, there is a progressive reduction in cytokeratin expression, desmosome formation, adherens junctions and focal adhesions, ultimately leading to poorly adhesive phenotype, which is associated with anchorage-independence. Surprisingly, unlike ‘‘conventional EMT’’, these changes are associated with reduced Rac1-dependent cell migration. We monitored reduced Rac1-dependent migration also in the cervical cancer cell line SiHa. Therefore we can conclude that up to the stage of tumor formation migratory activity is eliminated. Citation: Geiger T, Sabanay H, Kravchenko-Balasha N