Suo Shiqi, Chen Song, Zhou Liyuan, Xu Ruili, Li Jingxia, Li Wei
Department of Gynecology, The Affiliated Hospital of Hebei University of Engineering, Handan, China.
Department of Orthopedics, The Affiliated Hospital of Hebei University of Engineering, Handan, China.
Histol Histopathol. 2025 Feb;40(2):215-223. doi: 10.14670/HH-18-767. Epub 2024 May 27.
Endometrial cancer (EC) is a prevalent gynecologic malignancy. The critical role of PTPN18 in EC has been reported, while its role in the aerobic glycolysis of EC cells remains unclear. Our current study focused on the mechanism of PTPN18 in the regulation of aerobic glycolysis in EC.
PTPN18 expression levels in endometrial stromal cells (KC02-44D) and EC cells (KLE, HEC-1-A, HEC-1B, and HEC-50) were determined. Following transfection of sh-PTPN18 in HEC-1-A cells, the changes in cell migratory and invasive abilities were assessed by the Transwell assay, and the changes in glucose consumption, lactic acid secretion, and ATP levels were detected using kits. The expression levels of glycolysis-related proteins HIF-1α, PKM2, and LDHA and the activation of the MYC/PI3K/AKT pathway were detected by Western blot. Additionally, sh-PTPN18 and pcDNA3.1-MYC were transfected into HEC-1-A cells to further explore their roles in the changes in aerobic glycolysis, migration, and invasion ability of EC cells.
Expression of PTPN18 in EC cells was up-regulated (HEC-1-A>HEC-1B>HEC-50>KLE). PTPN18 knockdown suppressed EC cell migration and invasion. Additionally, PTPN18 knockdown reduced glucose consumption, lactate production, ATP levels, and glycolysis-related protein levels (HIF-1α, PKM2, LDHA). PTPN18 knockdown inhibited the activation of the MYC/PI3K/AKT pathway in EC cells. MYC overexpression partially annulled the inhibitory effects of PTPN18 knockdown on aerobic glycolysis, migration, and invasion of EC cells.
Our present study provided evidence that the knockdown of PTPN18 inhibited the aerobic glycolysis, migration, and invasion of EC cells by suppressing the MYC/PI3K/AKT pathway.
子宫内膜癌（EC）是一种常见的妇科恶性肿瘤。已有报道称PTPN18在EC中起关键作用，但其在EC细胞有氧糖酵解中的作用仍不清楚。我们目前的研究聚焦于PTPN18调控EC细胞有氧糖酵解的机制。
测定子宫内膜基质细胞（KC02 - 44D）和EC细胞（KLE、HEC - 1 - A、HEC - 1B和HEC - 50）中PTPN18的表达水平。在HEC - 1 - A细胞中转染sh - PTPN18后，通过Transwell实验评估细胞迁移和侵袭能力的变化，并使用试剂盒检测葡萄糖消耗、乳酸分泌和ATP水平的变化。通过蛋白质免疫印迹法检测糖酵解相关蛋白HIF - 1α、PKM2和LDHA的表达水平以及MYC/PI3K/AKT通路的激活情况。此外，将sh - PTPN18和pcDNA3.1 - MYC转染到HEC - 1 - A细胞中，以进一步探究它们在EC细胞有氧糖酵解、迁移和侵袭能力变化中的作用。
PTPN18在EC细胞中的表达上调（HEC - 1 - A>HEC - 1B>HEC - 50>KLE）。敲低PTPN18可抑制EC细胞的迁移和侵袭。此外，敲低PTPN18可降低葡萄糖消耗、乳酸生成、ATP水平以及糖酵解相关蛋白水平（HIF - 1α、PKM2、LDHA）。敲低PTPN18可抑制EC细胞中MYC/PI3K/AKT通路的激活。MYC过表达部分消除了敲低PTPN18对EC细胞有氧糖酵解、迁移和侵袭的抑制作用。
我们目前的研究表明，敲低PTPN18通过抑制MYC/PI3K/AKT通路抑制了EC细胞的有氧糖酵解、迁移和侵袭。
