Zhang Jiayu, Peng Jianmin, Wang Siyu, Wang Li, Sun Yutong, Xia Juan, Cheng Bin, Hu Qinchao
Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, China.
Cell Death Discov. 2025 Jan 28;11(1):30. doi: 10.1038/s41420-025-02314-1.
Emerging evidence shows that lipid metabolic reprogramming plays a vital role in tumor metastasis. The effect and mechanism of fatty acids and lipid droplets (LDs), the core products of lipid metabolism, on the metastasis of oral squamous cell carcinoma (OSCC), need further exploration. In this study, the influence of palmitic acid (PA) and oleic acid (OA) on the migration and invasion ability of OSCC cells was determined by in vitro experiments. Genetic manipulation of PLIN2 was performed to explore its effect on the accumulation of LDs and OSCC metastasis. Possible mechanisms of these biological effects were clarified by detecting the levels of epithelial-mesenchymal transition (EMT) markers and phosphatidylinositol 3-kinase (PI3K) pathway proteins as well as conducting various bioinformatics analyses. The results indicated that PA/OA promoted the migration and invasion of OSCC cells and induced PLIN2-dependent LDs accumulation in vitro. Knockdown of PLIN2 inhibited the LDs accumulation and the migration and invasion of OSCC cells in vitro, while overexpression of PLIN2 enhanced those of OSCC cells in vitro and also promoted the metastasis of OSCC in vivo. Besides, PLIN2 up-regulation activated the PI3K pathway and subsequently enhanced EMT in OSCC cells in vitro. OSCC patients with higher PLIN2 expression possessed poorer prognosis and higher sensitivity to chemotherapy drugs (1S,3 R)-RSL3 and ML-210. In conclusion, PLIN2-dependent LDs accumulation could promote the metastasis of OSCC cells by regulating EMT. PLIN2 might be a potential therapeutic target for OSCC patients, especially those with obesity.
新出现的证据表明，脂质代谢重编程在肿瘤转移中起着至关重要的作用。脂肪酸和脂滴（LDs）作为脂质代谢的核心产物，对口腔鳞状细胞癌（OSCC）转移的影响及机制尚需进一步探索。在本研究中，通过体外实验确定了棕榈酸（PA）和油酸（OA）对OSCC细胞迁移和侵袭能力的影响。对PLIN2进行基因操作，以探讨其对LDs积累和OSCC转移的影响。通过检测上皮-间质转化（EMT）标志物和磷脂酰肌醇3-激酶（PI3K）通路蛋白水平以及进行各种生物信息学分析，阐明了这些生物学效应的可能机制。结果表明，PA/OA促进了OSCC细胞的迁移和侵袭，并在体外诱导了PLIN2依赖性的LDs积累。敲低PLIN2可抑制体外LDs积累以及OSCC细胞的迁移和侵袭，而PLIN2的过表达则增强了体外OSCC细胞的迁移和侵袭能力，并促进了体内OSCC的转移。此外，PLIN2上调激活了PI3K通路，随后增强了体外OSCC细胞的EMT。PLIN2表达较高的OSCC患者预后较差，对化疗药物（1S,3 R）-RSL3和ML-210的敏感性较高。总之，PLIN2依赖性的LDs积累可通过调节EMT促进OSCC细胞的转移。PLIN2可能是OSCC患者，尤其是肥胖患者的潜在治疗靶点。
