PKD3 promotes metastasis and growth of oral squamous cell carcinoma through positive feedback regulation with PD-L1 and activation of ERK-STAT1/3-EMT signalling.
10.1038/s41368-021-00112-w
- Author:
Bomiao CUI
1
;
Jiao CHEN
1
;
Min LUO
1
;
Yiying LIU
1
;
Hongli CHEN
1
;
Die LÜ
1
;
Liwei WANG
1
;
Yingzhu KANG
1
;
Yun FENG
1
;
Libin HUANG
2
;
Ping ZHANG
3
Author Information
1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China.
2. Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. huanglibin525@163.com.
3. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China. pingzhang68@hotmail.com.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Animals;
B7-H1 Antigen/metabolism*;
Carcinoma, Squamous Cell;
Cell Line, Tumor;
Feedback;
Head and Neck Neoplasms;
Humans;
Mice;
Mouth Neoplasms;
Protein Kinase C;
STAT1 Transcription Factor;
Squamous Cell Carcinoma of Head and Neck
- From:
International Journal of Oral Science
2021;13(1):8-8
- CountryChina
- Language:English
-
Abstract:
Oral squamous cell carcinoma (OSCC) has a high incidence of metastasis. Tumour immunotherapy targeting PD-L1 or PD-1 has been revolutionary; however, only a few patients with OSCC respond to this treatment. Therefore, it is essential to gain insights into the molecular mechanisms underlying the growth and metastasis of OSCC. In this study, we analysed the expression levels of protein kinase D3 (PKD3) and PD-L1 and their correlation with the expression of mesenchymal and epithelial markers. We found that the expression of PKD3 and PD-L1 in OSCC cells and tissues was significantly increased, which correlated positively with that of mesenchymal markers but negatively with that of epithelial markers. Silencing PKD3 significantly inhibited the growth, metastasis and invasion of OSCC cells, while its overexpression promoted these processes. Our further analyses revealed that there was positive feedback regulation between PKD3 and PD-L1, which could drive EMT of OSCC cells via the ERK/STAT1/3 pathway, thereby promoting tumour growth and metastasis. Furthermore, silencing PKD3 significantly inhibited the expression of PD-L1, and lymph node metastasis of OSCC was investigated with a mouse footpad xenograft model. Thus, our findings provide a theoretical basis for targeting PKD3 as an alternative method to block EMT for regulating PD-L1 expression and inhibiting OSCC growth and metastasis.
