Prostaglandin E receptor 3 (PTGER3) is involved in a variety of biological processes in the human body and is closely associated with the development and progression of a variety of cancer types. However, the role of PTGER3 in triple‐negative breast cancer (TNBC) remains unclear. In the present study, low PTGER3 expression was found to be associated with poor prognosis in TNBC patients. PTGER3 plays a crucial role in regulating TNBC cell invasion, migration, and proliferation. Upregulation of PTGER3 weakens the epithelial–mesenchymal phenotype in TNBC and promotes ferroptosis both in vitro and in vivo by repressing glutathione peroxidase 4 (GPX4) expression. On the other hand, downregulation of PTGER3 inhibits ferroptosis by increasing GPX4 expression and activating the PI3K‐AKT pathway. Upregulation of PTGER3 also enhances the sensitivity of TNBC cells to paclitaxel. Overall, this study has elucidated critical pathways in which low PTGER3 expression protects TNBC cells from undergoing ferroptosis, thereby promoting its progression. PTGER3 may thus serve as a novel and promising biomarker and therapeutic target for TNBC.

中文翻译：

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PTGER3 敲低抑制三阴性乳腺癌对铁死亡的脆弱性

前列腺素E受体3（PTGER3）参与人体内多种生物过程，与多种癌症的发生、发展密切相关。然而，PTGER3 在三阴性乳腺癌 (TNBC) 中的作用仍不清楚。在本研究中，发现 PTGER3 低表达与 TNBC 患者预后不良相关。 PTGER3 在调节 TNBC 细胞侵袭、迁移和增殖中发挥着至关重要的作用。 PTGER3 的上调削弱了 TNBC 中的上皮-间质表型，并通过抑制谷胱甘肽过氧化物酶 4 (GPX4) 的表达促进体外和体内的铁死亡。另一方面，PTGER3 的下调通过增加 GPX4 表达并激活 PI3K-AKT 通路来抑制铁死亡。 PTGER3 的上调还增强了 TNBC 细胞对紫杉醇的敏感性。总体而言，这项研究阐明了 PTGER3 低表达保护 TNBC 细胞免遭铁死亡的关键途径，从而促进其进展。因此，PTGER3 可能作为 TNBC 的一种新颖且有前途的生物标志物和治疗靶点。