title: Src family kinase inhibitor PP2 accelerates differentiation in human intestinal epithelial cells.
abstract: 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 HNF1α 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.
authors.affiliation: Laboratory of Intestinal Physiopathology, Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Amira
authors.initials: A
authors.lastname: Seltana
authors.forename: Amel
authors.initials: A
authors.lastname: Guezguez
authors.forename: Manon
authors.initials: M
authors.lastname: Lepage
authors.forename: Nuria
authors.initials: N
authors.lastname: Basora
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Beaulieu
mesh_terms: D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D007422:Intestines / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: C412373:AG 1879; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines; D014157:Transcription Factors; D019061:src-Family Kinases