SOX2-dependent expression of dihydroorotate dehydrogenase regulates oral squamous cell carcinoma cell proliferation / 国际口腔科学杂志·英文版
International Journal of Oral Science
;
(4): 3-3, 2021.
Article
in English
| WPRIM
| ID: wpr-880857
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Mouth Neoplasms
/
Carcinoma, Squamous Cell
/
Oxidoreductases Acting on CH-CH Group Donors
/
Cell Proliferation
/
SOXB1 Transcription Factors
/
Squamous Cell Carcinoma of Head and Neck
/
Head and Neck Neoplasms
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
International Journal of Oral Science
Year:
2021
Type:
Article
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