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

被引：16

作者：

Seltana, Amira ^{[1
]}

Guezguez, Amel ^{[1
]}

Lepage, Manon ^{[1
]}

Basora, Nuria ^{[1
]}

Beaulieu, Jean-Francois ^{[1
]}

机构：

[1] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Anat & Biol Cellulaire, Lab Intestinal Physiopathol, Sherbrooke, PQ J1H 5N4, Canada

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2013年 / 430卷 / 04期

基金：

加拿大健康研究院;

关键词：

Src kinase; Cell differentiation; Intestine; Human; Caco-2; cells; Cdx2; HNF1; alpha; H3K27me3; SUCRASE-ISOMALTASE EXPRESSION; TRANSIENT MOSAIC PATTERNS; HUMAN COLON; STEM-CELLS; E-CADHERIN; PROTEIN; ACTIVATION; CDX2; GATA-4; P38;

D O I：

10.1016/j.bbrc.2012.12.085

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 alpha 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. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：1195 / 1200

页数：6

共 44 条

[1]

Babyastsky M.W., 1999, Gastroenterology, P547

[2]

BEAULIEU JF, 1989, J BIOL CHEM, V264, P20000

[3] CLONAL ANALYSIS OF SUCRASE ISOMALTASE EXPRESSION IN THE HUMAN COLON ADENOCARCINOMA CACO-2 CELLS [J].