Chen Sihan, Li Zhangyun, Wang Yanyan, Fan Shaohua
School of Life Science, Jiangsu Normal University, Xuzhou, China.
Department of Ultrasonic Medicine, The First People's Hospital of Xuzhou, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, China.
Front Oncol. 2022 Aug 17;12:952425. doi: 10.3389/fonc.2022.952425. eCollection 2022.
Butyrophilin Subfamily 3 Member A3 (BTN3A3) is a type I transmembrane protein belonging to the immunoglobulin (Ig) superfamily, which is expressed in many cancers. Clinical data show that ovarian cancer patients with high expression of have a longer survival time, but the mechanism of BTN3A3 in the occurrence and progression of ovarian cancer is still unclear. Here, we found that knockdown can promote the proliferation, migration and invasion of ovarian cancer cells, while overexpression of can inhibit the proliferation, migration and invasion of ovarian cancer cells. We analyzed the immunoprecipitated BTN3A3 complex by mass spectrometry and found that BTN3A3 binds to FGF2, and the overexpression of leads to a decrease in the protein level of FGF2, which in turn leads to a decrease in the level of phosphorylation of ERK1/2. By increasing the protein level of FGF2, it was found that the level of ERK1/2 phosphorylation also increased. Finally, the cancer promotion phenomenon caused by knockdown can be improved by using ERK1/2 inhibitor SCH772984. To sum up, BTN3A3 interacts with FGF2, which inhibits FGF2/ERK1/2 axis and ultimately inhibits the proliferation, migration and invasion of ovarian cancer cells. Our results suggest that BTN3A3 may be a prognostic marker and a potential therapeutic target for ovarian cancer.
嗜乳脂蛋白亚家族3成员A3（BTN3A3）是一种属于免疫球蛋白（Ig）超家族的I型跨膜蛋白，在多种癌症中均有表达。临床数据显示，BTN3A3高表达的卵巢癌患者生存时间更长，但BTN3A3在卵巢癌发生发展中的机制仍不清楚。在此，我们发现敲低BTN3A3可促进卵巢癌细胞的增殖、迁移和侵袭，而BTN3A3过表达则可抑制卵巢癌细胞的增殖、迁移和侵袭。我们通过质谱分析免疫沉淀的BTN3A3复合物，发现BTN3A3与FGF2结合，BTN3A3过表达导致FGF2蛋白水平降低，进而导致ERK1/2磷酸化水平降低。通过增加FGF2蛋白水平，发现ERK1/2磷酸化水平也升高。最后，使用ERK1/2抑制剂SCH772984可改善敲低BTN3A3所导致的促癌现象。综上所述，BTN3A3与FGF2相互作用，抑制FGF2/ERK1/2轴，最终抑制卵巢癌细胞的增殖、迁移和侵袭。我们的结果表明，BTN3A3可能是卵巢癌的一个预后标志物和潜在治疗靶点。
