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GPAT3 Promotes Oral Squamous Cell Carcinoma Invasion by Reprogramming Lipid Metabolism
Zixian Li1,2, Zhiheng Yang1,2, Xiren Wang1,3
1Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
Background:
Although Glycerol-3-phosphate acyltransferase 3 (GPAT3)-mediated lipid metabolic reprogramming has been recognized as a driver of tumor progression, its prognostic significance and underlying mechanisms in oral squamous cell carcinoma (OSCC) remain to be fully elucidated.
Methods:
This retrospective study included 77 primary OSCC samples, expression pattern of GPAT3 and the prognostic value were analyzed by immunohistochemistry. In vitro functional experiments included cell viability and cell migration. Gene and protein expressions was analyzed via immunofluorescence staining, flow cytometry, RT-PCR, and western blotting. Lipids profiles were determined by mass spectrometry.
Results:
GPAT3 was broadly expressed in tumor cells, fibroblast-like cells, and tumor-infiltrating lymphocytes, with significantly higher expression at the invasive tumor front than in the tumor center. Elevated GPAT3 expression was positively correlated with adverse clinical outcomes and poor prognosis. In vitro experiments showed that both GPAT3 knockdown and overexpression markedly altered OSCC cell proliferation and migration. GPAT3 inhibition reduced the levels of several phospholipids, including Cer, PS, PE, and PC, accompanied by decreased expression of the invasion-related proteins p-FAK and p-Myosin II.
Conclusion:
GPAT3 regulates the invasive behavior of OSCC by mediating lipid metabolic reprogramming, serving as a biomarker for the clinical prognosis of OSCC patients.