Src family kinase inhibitor PP2 accelerates differentiation in human intestinal epithelial cells

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• 作者：Amira Seltana¹ ; Amel Guezguez¹ ; Manon Lepage ; Nuria Basora ; Jean-Franç ; ois Beaulieu ; ^{Jean-Francois.Beaulieu@USherbrooke.ca}
• 关键词：Src kinase ; Cell differentiation ; Intestine ; Human ; Caco-2 cells ; Cdx2 ; HNF1¦Á ; H3K27me3
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：25 January, 2013
• 年：2013
• 卷：430
• 期：4
• 页码：1195-1200
• 全文大小：579 K

文摘

The proto-oncogene Src is an important protein tyrosine kinase involved in signaling pathways that control cell adhesion, growth, migration and survival. Here, we investigated the involvement of Src family kinases (SFKs) in human intestinal cell differentiation. We first observed that Src activity peaked in early stages of Caco-2/15 cell differentiation. Inhibition of SFKs with PP2, a selective SFK inhibitor, accelerated the overall differentiation program. Interestingly, all polarization and terminal differentiation markers tested, including sucrase-isomaltase, lactase-phlorizin hydrolase and E and Li-cadherins were found to be significantly up-regulated after only 3 days of treatment in the newly differentiating cells. Further investigation of the effects of PP2 revealed a significant up-regulation of the two main intestinal epithelial cell-specific transcription factors Cdx2 and HNF1¦Á and a reduction of polycomb PRC2-related epigenetic repressing activity as measured by a decrease in H3K27me3, two events closely related to the control of cell terminal differentiation in the intestine. Taken together, these data suggest that SFKs play a key role in the control of intestinal epithelial cell terminal differentiation.