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SCF/C-Kit/JNK/AP-1 Signaling Pathway Promotes Claudin-3 Expression in Colonic Epithelium and Colorectal Carcinoma
- Source :
- International Journal of Molecular Sciences; Volume 18; Issue 4; Pages: 765, International Journal of Molecular Sciences, Vol 18, Iss 4, p 765 (2017), International Journal of Molecular Sciences
- Publication Year :
- 2017
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2017.
-
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.
- Subjects :
- 0301 basic medicine
activator protein-1
Recombinant Human Stem Cell Factor
lcsh:Chemistry
Mice
0302 clinical medicine
Intestinal Mucosa
lcsh:QH301-705.5
Spectroscopy
c-Jun N-terminal kinase
Stem Cell Factor
Tight junction
Kinase
General Medicine
Intestinal epithelium
Computer Science Applications
Gene Expression Regulation, Neoplastic
Proto-Oncogene Proteins c-kit
medicine.anatomical_structure
030220 oncology & carcinogenesis
claudins
colorectal cancer
c-kit
claudin-3
Signal transduction
Colorectal Neoplasms
HT29 Cells
MAP Kinase Signaling System
Biology
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Cell Line, Tumor
medicine
Animals
Humans
Physical and Theoretical Chemistry
Claudin
Molecular Biology
Organic Chemistry
Molecular biology
Epithelium
digestive system diseases
Transcription Factor AP-1
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Chromatin immunoprecipitation
Neoplasm Transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences; Volume 18; Issue 4; Pages: 765
- Accession number :
- edsair.doi.dedup.....5b44a776156e958384456d6800d553ba
- Full Text :
- https://doi.org/10.3390/ijms18040765