期刊
JOURNAL OF CANCER
卷 10, 期 23, 页码 5770-5784出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.29838
关键词
OSCC; B7-H3; glycolysis; immunoregulatory protein; PI3K/Akt/mTOR pathway
类别
资金
- Program of Science and Technology Department of Sichuan Province [0040305302018, 0040305301484]
- Sichuan University [20826041A4164]
- West China Hospital of Stomatology [RD-02-201909]
- National Natural Science Foundation of China [81902775]
OSCC (oral squamous carcinoma) is one of most common malignant cancer. Although previous studies have found abnormal expression of B7-H3 in human OSCC, the exact role and molecular mechanism of B7-H3 in OSCC remain unknown. In this study, we investigated the role of B7-H3 in glucose metabolic reprogramming of OSCC cells in vitro and in vivo. We first detected the expression of B7-H3 in OSCC samples. Next, siRNAs and overexpression short-hairpin RNA of B7-H3 were transfected into SCC25 and Ca127 cells, and cell proliferation, migration and invasion were analyzed via CCK8, colony formation and transwell assays. Then glycolysis flux was determined through measuring glucose uptake and lactate production, and mRNA and protein expression levels were determined by real-time quantitative PCR and western blot respectively. The results presented here showed B7-H3 was upregulated in OSCC samples compared with normal tissues, and the expression level was associated with tumor size and nodal metastasis. B7-H3 affects OSCC cell proliferation, migration and invasion. We also found that B7-H3 promoted the Warburg effect, evidenced by increase glucose uptake and lactate production. We further demonstrated that B7-H3 enhanced OSCC glycolysis through the upregulation of HIF-1 alpha and its downstream targets, Glutl and PFKFB3, which are key factors in glycolysis. Mechanically, we demonstrated that B7-H3 regulates HIF-1 alpha expression through PI3K/Akt/mTOR pathway. Metabolic imaging of human OSCC cancer xenograft in mice confirmed that B7-H3 enhanced tumor glucose uptake, glycolysis promoted genes expression and tumor growth. Taken together, our results have unveiled a mechanism that B7-H3 drives OSCC progression through enhancing of glycolytic metabolic program in OSCC.
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