- 作者: Hsiao-Chin Chou, Chun-Mei Cheng, Chi-Hwa Yang, Tzu-Yin Lin, Ya-Wen Liu, Tse-Hua Tan & Yi-Rong Chen
- 作者服務機構: 1. Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA 2.Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan 3.Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, 35053, Taiwan
- 中文摘要:
- 英文摘要:
Background: Tight junctions (TJ) are multi-protein complexes that hold epithelial cells together and form structural
and functional barriers for maintaining proper biological activities. Dual specifcity phosphatase 3 (DUSP3), a suppres‑
sor of multiple protein tyrosine (Tyr) kinases, is decreased in lung cancer tissues. Here we demonstrated the role of
DUSP3 in regulation of epithelial TJ.
Methods: Barrier functions of TJ were examined in wild-type or DUSP3-defcient lung epithelial cells. Animal and
clinical data were analyzed for the association between DUSP3 defciency and lung cancer progression. Proximity liga‑
tion assay, immunoblotting, and phosphatase assay were performed to study the efect of DUSP3 on the TJ protein
occludin (OCLN). Mutations of Tyr residues on OCLN showed the role of Tyr phosphorylation in regulating OCLN.
Results: Compared to those of the DUSP3-expressing cells, we found the expression and distribution of ZO-1, a
TJ-anchoring molecule, were abnormal in DUSP3-defcient cells. OCLN had an increased phosphorylation level in
DUSP3-defcient cells. We identifed that OCLN is a direct substrate of DUSP3. DUSP3 regulated OCLN ubiquitination
and degradation through decreasing OCLN tyrosine phosphorylation directly or through suppressing focal adhesion
kinase, the OCLN kinase.
Conclusion: Our study revealed that DUSP3 is an important TJ regulatory protein and its decrease may be involved
in progression of epithelial cancers. - 中文關鍵字:
- 英文關鍵字: DUSP3/VHR, Epithelium, FAK, Occludin, Tight junction