TRPP2 regulates the migration and invasion of oral squamous cell carcinoma through the UPR/AFT6/EpCAM signaling pathway
10.19405/j.cnki.issn1000-1492.2024.11.018
- Author:
Zhuzhu Liang
1
;
Shu Chen
1
;
Qianyu Sun
1
;
Bing Shen
2
;
Haowei Xue
1
Author Information
1. Dept of Oral and Maxillofacial Surgery , The First Afiliated Hospital of Anhui Medical University , Hefei 230022
2. State Key Laboratory of Quality Research in Chinese Medicine , Macau University of Science and Technology , Macao SAR 999078
- Publication Type:Journal Article
- Keywords:
oral squamous cell carcinoma;
transient receptor potential polycystic 2;
unfolded protein response;
endoplasmic reticulumepithelial stress;
cell adhesion molecule;
cell migration and invasion
- From:
Acta Universitatis Medicinalis Anhui
2024;59(11):2024-2032,2064
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the expression of transient receptor polycystic protein 2(TRPP2) in oral squamous epithelial cell and its effect on the invasion and migration of oral squamous cell carcinoma(OSCC), and to explore the potential signaling pathway of TRPP2 affecting OSCC metastasis.
Methods:The OSCC model with TRPP2 knockdown was constructed by CRISPR-Cas9 lentivirus plasmid transfection technique. The effect of TRPP2 protein knockdown was verified by Western blot. The effect of TRPP2 on OSCC proliferation was detected by CCK-8 assay and clone formation assay. RT-qPCR was used to detect the target genes associated with TRPP2 metastasis to OSCC. Western blot and RT-qPCR were used to detect the expression of EpCAM and its transcription factors associated with unfolded protein response(UPR). The effects of TRPP2 on the invasion and migration of OSCC were examined by invasion test and scratch test.
Results:Compared with HOK in oral epithelial cells, the expression of TRPP2 in OSCC was significantly higher. When TRPP2 was knocked down, OSCC proliferation and clonalformation were significantly enhanced. Compared with the control group, a total of 494 differential genes were significantly expressed in TRPP2 knockdown transcription profile, among which 234 genes were up-regulated and 260 genes were down-regulated. The expression of EpCAM gene, which is related to cell adhesion, was up-regulated. In addition, UPR related genes PERK, ATF6, GRP78 were up-regulated, while ATF6 and EpCAM were down-regulated in OSCC compared to HOK cells. The expression of ATF6 and EpCAM in oral squamous cell carcinoma cells was up-regulated by TRPP2 knockdown, and the cell migration and invasion ability decreased. The ATF6 inhibitor ceapin-A7(5 μmol/L) restored the OSCC migration and invasion ability of TRPP2 knockdown.
Conclusion:TRPP2 is highly expressed in OSCC. When TRPP2 is knocked down, OSCC proliferation ability is enhanced, migration and invasion ability are inhibited. TRPP2 mediates the expression of EpCAM through activation of UPR, thus affecting the invasion and migration of oral squamous cell carcinoma.
- Full text:2024122614111576343TRPP2通过UPR_AF...口腔鳞状细胞癌的迁移和侵袭_梁珠珠.pdf
