NudCL2 suppresses pancreatic cancer progression by inhibiting SLC7A11-mediated EMT and metastasis

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2025-09-01 DOI:10.1016/j.yexcr.2025.114730

Jiaxing Feng , Mingyang Yang , Rijin Lin , Kaifeng Shang , Meng Sun , Zijie Guo , Yanting Wang , Tianhua Zhou , Feng Yang , Yuehong Yang

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引用次数: 0

Abstract

Pancreatic cancer (PC) is a highly aggressive malignancy with limited therapeutic options and poor prognosis. NudC-like protein 2 (NudCL2), a molecular cochaperone of HSP90, has been implicated in various cellular processes; however, its role in pancreatic cancer remains poorly understood. In this study, we report that NudCL2 expression is significantly downregulated in PC tissues and is correlated with poor patient survival. The results of functional assays revealed that NudCL2 knockdown enhances cell invasion and migration in vitro and promotes lung and liver metastases in vivo. Further analysis revealed solute carrier family 7 member 11 (SLC7A11) as a key downstream effector that was upregulated upon NudCL2 depletion. Suppression of SLC7A11 reversed the increase in cell motility induced by NudCL2 depletion. Mechanistically, our findings suggest that NudCL2 regulates the transcriptional activity of SLC7A11 and that the NudCL2/SLC7A11 axis may suppress cell motility by inhibiting the epithelial-mesenchymal transition (EMT) pathway. Collectively, these results highlight the important role of NudCL2 in PC progression through the modulation of EMT via SLC7A11, providing valuable insights into its potential as both a therapeutic target and a prognostic biomarker.

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NudCL2通过抑制slc7a11介导的EMT和转移来抑制胰腺癌的进展

胰腺癌（PC）是一种高度侵袭性的恶性肿瘤，治疗选择有限，预后差。nudc样蛋白2 （NudCL2）是HSP90的分子伴侣，参与多种细胞过程；然而，它在胰腺癌中的作用仍然知之甚少。在这项研究中，我们报道了NudCL2在PC组织中的表达显著下调，并与患者生存率低相关。功能分析结果显示，敲低NudCL2可增强体外细胞的侵袭和迁移，促进体内肺和肝转移。进一步分析发现，溶质载体家族7成员11 （SLC7A11）是一个关键的下游效应因子，在NudCL2缺失时上调。SLC7A11的抑制逆转了NudCL2缺失引起的细胞运动的增加。在机制上，我们的研究结果表明，NudCL2调节SLC7A11的转录活性，并且NudCL2/SLC7A11轴可能通过抑制上皮-间质转化（EMT）途径来抑制细胞运动。总的来说，这些结果强调了NudCL2通过SLC7A11调节EMT在PC进展中的重要作用，为其作为治疗靶点和预后生物标志物的潜力提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.