KLF4 regulation in intestinal epithelial cell maturation.
KLF4 regulation in intestinal epithelial cell maturation.
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DOI：
10.1016/j.yexcr.2008.10.004
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发表时间：
2008-12-10
影响因子：
3.7
通讯作者：
Augenlicht LH
中科院分区：
文献类型：
--
作者：
Flandez M;Guilmeau S;Blache P;Augenlicht LH
kr<s:1> ppel样因子4 （KLF4）转录因子抑制胃肠道上皮的肿瘤发生。因此，它在胃癌和结肠癌中的表达减少。此外，KLF4调节分化和生长，这可能是其肿瘤抑制活性的基础。我们解剖了Klf4在正常小鼠肠上皮沿隐窝绒毛和头尾轴的表达。Klf4在绒毛的分化细胞中达到最高水平，在十二指肠bbb、空肠bbb、回肠bbb中的水平与这些区域的杯状细胞的表现呈反比，而这些区域的谱系先前与Klf4有关。同时，使用HT29cl的体外研究。16E和Caco2结肠癌细胞系表明，KLF4分别随着杯状细胞系和吸收细胞系的分化而增加，KLF4水平在短链脂肪酸丁酸诱导的分化过程中也增加，与细胞命运无关。此外，我们确定肠上皮增殖室中KLF4的低水平表达受转录因子TCF4和SOX9的调控，它们分别是β-catenin/Tcf信号的效应因子和靶标因子，独立于CDX2。因此，结肠肿瘤中KLF4抑瘤活性的降低可能是由升高的β-catenin/Tcf信号驱动的。
The Krüppel-like factor 4 (KLF4) transcription factor suppresses tumorigenesis in gastrointestinal epithelium. Thus, its expression is decreased in gastric and colon cancers. Moreover, KLF4 regulates both differentiation and growth that is likely fundamental to its tumor suppressor activity. We dissected the expression of Klf4 in the normal mouse intestinal epithelium along the crypt-villus and cephalo-caudal axes. Klf4 reached its highest level in differentiated cells of the villus, with levels in the duodenum > jejunum > ileum, in inverse relation to the representation of goblet cells in these regions, the lineage previously linked to KLF4. In parallel, in vitro studies using HT29cl.16E and Caco2 colon cancer cell lines clarified that KLF4 increased coincident with differentiation along both the goblet and absorptive cell lineages, respectively, and that KLF4 levels also increased during differentiation induced by the short chain fatty acid butyrate, independently of cell fate. Moreover, we determined that lower levels of KLF4 expression in the proliferative compartment of the intestinal epithelium are regulated by the transcription factors TCF4 and SOX9, an effector and a target, respectively, of β-catenin/Tcf signaling, and independently of CDX2. Thus, reduced levels of KLF4 tumor suppressor activity in colon tumors may be driven by elevated β-catenin/Tcf signaling.
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DOI：
10.1083/jcb.200311021
发表时间：
2004-07-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Blache P;van de Wetering M;Duluc I;Domon C;Berta P;Freund JN;Clevers H;Jay P
通讯作者：
Jay P
DOI：
10.1152/ajpgi.00203.2003
发表时间：
2004-01-01
影响因子：
4.5
作者：
Hinnebusch, BF;Siddique, A;Hodin, RA
通讯作者：
Hodin, RA
影响因子：
12.3
作者：
Kaczynski J;Cook T;Urrutia R
通讯作者：
Urrutia R
影响因子：
5.3
作者：
De Santa Barbara, P;Bonneaud, N;Berta, P
通讯作者：
Berta, P
影响因子：
4.8
作者：
Liu, SG;Guo, R;Quarles, LD
通讯作者：
Quarles, LD