LPCAT1 Promotes Cutaneous Squamous Cell Carcinoma via EGFR-Mediated Protein Kinase B/p38MAPK Signaling Pathways
LPCAT1 Promotes Cutaneous Squamous Cell Carcinoma via EGFR-Mediated Protein Kinase B/p38MAPK Signaling Pathways
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LPCAT1 通过 EGFR 介导的 AKT/p38MAPK 信号通路促进皮肤鳞状细胞癌
DOI：
10.1016/j.jid.2021.07.163
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发表时间：
2022-01-20
影响因子：
6.5
通讯作者：
Zheng, Yan
中科院分区：
文献类型：
--
作者：
Huang, Yingjian;Wang, Yuqian;Zheng, Yan
皮肤鳞状细胞癌 (cSCC) 是第二常见的皮肤癌。 LPCAT1 是一种溶血磷脂酰胆碱酰基转移酶，在膜脂重塑中占据中心地位。 LPCAT1 在多种癌症中升高并促进癌症的发展。然而，其在 cSCC 中的作用和分子机制仍有待阐明。在这项研究中，我们发现 LPCAT1 在 cSCC 组织和细胞系中表达上调。体外功能丧失和功能获得实验表明，LPCAT1 促进 cSCC 细胞增殖、保护细胞免于凋亡、加速上皮间质转化并增强细胞转移。从机制上讲，LPCAT1 调节 EGFR 信号传导。在 cSCC 中，LPCAT1 的致癌作用是由 EGFR/蛋白激酶 B 和 EGFR/p38MAPK 通路介导的。使用异种移植小鼠模型，我们整合了前面提到的结果。总之，LPCAT1 通过 EGFR 介导的蛋白激酶 B 和 p38MAPK 信号通路促进 cSCC 进展。 LPCAT1 可作为 cSCC 治疗干预的靶点。
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer. LPCAT1, a lysophosphatidylcholine acyltransferase, takes a center stage in membrane lipid remodeling. LPCAT1 is elevated in several cancers and contributes to cancer development. However, its role and molecular mechanisms in cSCC remain to be elucidated. In this study, we found that LPCAT1 was upregulated in cSCC tissues and in cell lines. In vitro, loss-of-function and gain-of-function experiments demonstrated that LPCAT1 facilitated cSCC cell proliferation, protected cells against apoptosis, accelerated epithelial-mesenchymal transition, and enhanced cell metastasis. Mechanistically, LPCAT1 regulated EGFR signaling. The oncogenic effect of LPCAT1 was mediated by EGFR/protein kinase B and EGFR/p38MAPK pathways in cSCC. Using the xenograft mouse model, we consolidated the results mentioned earlier. In conclusion, LPCAT1 contributed to cSCC progression through EGFR-mediated protein kinase B and p38MAPK signaling pathways. LPCAT1 may serve as a target for therapeutic intervention in cSCC.