SOX2-dependent expression of dihydroorotate dehydrogenase regulates oral squamous cell carcinoma cell proliferation.
10.1038/s41368-020-00109-x
- Author:
Xuemei QIU
1
;
Sheng JIANG
2
;
Yanxuan XIAO
1
;
Yumin HE
1
;
Tao REN
3
;
Lu JIANG
4
;
Rui LIU
5
;
Qianming CHEN
1
Author Information
1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
2. Ministry of science and technology, The Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital), Chengdu, China.
3. Oncology Department, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China. rentao509@cmc.edu.cn.
4. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China. jianglu@scu.edu.cn.
5. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China. liurui_scu@hotmail.com.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Carcinoma, Squamous Cell;
Cell Proliferation;
Head and Neck Neoplasms;
Humans;
Mouth Neoplasms;
Oxidoreductases Acting on CH-CH Group Donors;
SOXB1 Transcription Factors;
Squamous Cell Carcinoma of Head and Neck
- From:
International Journal of Oral Science
2021;13(1):3-3
- CountryChina
- Language:English
-
Abstract:
Oral squamous cell carcinoma (OSCC) become a heavy burden of public health, with approximately 300 000 newly diagnosed cases and 145 000 deaths worldwide per year. Nucleotide metabolism fuel DNA replication and RNA synthesis, which is indispensable for cell proliferation. But how tumor cells orchestrate nucleotide metabolic enzymes to support their rapid growth is largely unknown. Here we show that expression of pyrimidine metabolic enzyme dihydroorotate dehydrogenase (DHODH) is upregulated in OSCC tissues, compared to non-cancerous adjacent tissues. Enhanced expression of DHODH is correlated with a shortened patient survival time. Inhibition of DHODH by either shRNA or selective inhibitors impairs proliferation of OSCC cells and growth of tumor xenograft. Further, loss of functional DHODH imped de novo pyrimidine synthesis, and disrupt mitochondrial respiration probably through destabilizing the MICOS complex. Mechanistic study shows that transcriptional factor SOX2 plays an important role in the upregulation of DHODH in OSCC. Our findings add to the knowledge of how cancer cells co-opt nucleotide metabolism to support their rapid growth, and thereby highlight DHODH as a potential prognostic and therapeutic target for OSCC treatment.
