文章：

L1CAM通过NF-κB激活促进人类子宫内膜癌的发展

L1CAM Promotes Human Endometrial Cancer Via NF-κB Activation

原文发布日期：8 January 2026

DOI: 10.3390/cancers18020198

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Endometrial cancer is one of the most common gynecological malignancies, with increasing incidence and mortality rates, particularly in developed countries. L1 cell adhesion molecule (L1CAM) has been identified as a poor prognostic factor for human endometrial cancer; however, the molecular mechanisms underlying its role in tumor progression remain unclear.Methods: We investigated the biological significance of L1CAM in human endometrial cancer using multiple cell lines. Functional analyses, including cell proliferation, cell cycle, and apoptosis assays, were performed afterL1CAMknockdown or overexpression.Results: L1CAM promoted the transition of endometrial cancer cells from the G0/G1 phase and enhanced cell proliferation.L1CAMknockdown inhibited NF-κB signaling by reducing NF-κB (p65) phosphorylation and downregulating the expression of downstream targets such asTNF. Overexpression of constitutively active IKKβ restored the proliferation defect caused byL1CAMknockdown, supporting the role of NF-κB as a key downstream effector of L1CAM. Immunohistochemical analysis revealed a significant correlation between L1CAM expression and nuclear NF-κB (p65) positivity rates in human patient samples. Furthermore, combination therapy with cisplatin and an IKK inhibitor enhanced the anti-proliferative effect.Conclusions: Our study demonstrated that L1CAM promotes proliferation and chemotherapy resistance in human endometrial cancer through activation of the NF-κB signaling pathway. Therapeutic strategies targeting the L1CAM-NF-κB pathway may represent a promising treatment option for improving prognosis in L1CAM-positive human endometrial cancer.

摘要翻译： 

背景/目的：子宫内膜癌是最常见的妇科恶性肿瘤之一，其发病率和死亡率逐年上升，在发达国家尤为显著。L1细胞粘附分子（L1CAM）已被确认为子宫内膜癌患者的不良预后因素，但其在肿瘤进展中的分子机制尚不明确。方法：我们利用多种细胞系研究了L1CAM在人子宫内膜癌中的生物学意义。通过敲低或过表达L1CAM，进行包括细胞增殖、细胞周期和凋亡实验在内的功能分析。结果：L1CAM促进了子宫内膜癌细胞从G0/G1期的转变并增强了细胞增殖能力。敲低L1CAM通过减少NF-κB（p65）的磷酸化和下调下游靶标如TNF的表达，抑制了NF-κB信号通路。过表达持续激活的IKKβ能够恢复因L1CAM敲低导致的增殖缺陷，证实了NF-κB作为L1CAM关键下游效应分子的作用。免疫组化分析显示，在临床患者样本中L1CAM表达与核NF-κB（p65）阳性率呈显著相关。此外，顺铂联合IKK抑制剂治疗增强了抗增殖效果。结论：本研究证明L1CAM通过激活NF-κB信号通路，促进人子宫内膜癌的增殖和化疗耐药性。针对L1CAM-NF-κB通路的治疗策略可能成为改善L1CAM阳性子宫内膜癌患者预后的有潜力的治疗选择。

原文链接：

L1CAM Promotes Human Endometrial Cancer Via NF-κB Activation