SCF-C-Kit-JNK-AP-1 Signaling Pathway Promotes Claudin-3 Expression in Colonic Epithelium and Colorectal CarcinomaReportar como inadecuado


SCF-C-Kit-JNK-AP-1 Signaling Pathway Promotes Claudin-3 Expression in Colonic Epithelium and Colorectal Carcinoma


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1

Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

2

Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China

3

Cancer Institute of Capital Medical University, Beijing 100069, China





*

Author to whom correspondence should be addressed.



Academic Editor: Atsushi Matsuzawa

Abstract Claudin-3 is a major protein of tight junctions TJs in the intestinal epithelium and is critical for maintaining cell-cell adhesion, barrier function, and epithelium polarity. Recent studies have shown high claudin-3 levels in several solid tumors, but the regulation mechanism of claudin-3 expression remains poorly understood. In the present study, colorectal cancer CRC tissues, HT-29 and DLD-1 CRC cell lines, CRC murine model C57BL-6 mice and c-kit loss-of-function mutant mice were used. We demonstrated that elevated claudin-3 levels were positively correlated with highly expressed c-kit in CRC tissues based upon analysis of protein expression. In vitro, claudin-3 expression was clearly increased in CRC cells by overexpressed c-kit or stimulated by exogenous recombinant human stem cell factor rhSCF, while significantly decreased by the treatment with c-kit or c-Jun N-terminal kinase JNK inhibitors. Chromatin immunoprecipitation ChIP and luciferase reporter assay showed that SCF-c-kit signaling significantly promoted activator protein-1 AP-1 binding with CLDN-3 promoter and enhanced its transcription activity. Furthermore, decreased expression of claudin-3 was obtained in the colonic epithelium from the c-Kit loss-of-function mutant mice. In conclusion, SCF-c-kit-JNK-AP-1 signaling pathway significantly promoted claudin-3 expression in colonic epithelium and CRC, which could contribute to epithelial barrier function maintenance and to CRC development. View Full-Text

Keywords: claudins; colorectal cancer; c-kit; claudin-3; c-Jun N-terminal kinase; activator protein-1 claudins; colorectal cancer; c-kit; claudin-3; c-Jun N-terminal kinase; activator protein-1





Autor: Yaxi Wang 1,2, Tingyi Sun 1,2,3, Haimei Sun 1,2,3, Shu Yang 1,2,3, Dandan Li 1,2 and Deshan Zhou 1,2,3,*

Fuente: http://mdpi.com/



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