Hou Zhichao, Ma Wenxia, Ren Dongliang, Shen Ningning, Bi Weilin, Guo Meiqin, Li Xinzheng, Wang Yanhong, Jia Hongyan
Department of Breast Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.
Department of Pathology, The Second Hospital of ShanXi Medical University, Tai Yuan, People's Republic of China.
J Inflamm Res. 2025 May 21;18:6467-6481. doi: 10.2147/JIR.S512905. eCollection 2025.
Breast cancer (BC) is the most common malignant tumor in women. Exportin-T (XPOT) which is a member of the karyopherin -β family has been identified as a prognostic biomarker in various cancers, but its role in BC remains inadequately understood. This study aims to investigate the clinical characterization and molecular mechanism of XPOT in BC.
A retrospective RNA-seq data analysis based on a cohort of 966 BC patients from The Cancer Genome Atlas database (TCGA) and 1904 patients from the Molecular Taxonomy of Breast Cancer International Consortium database was conducted for analyzing the correlation between XPOT expression and BC clinical pathological features. In addition, small interfering RNA transfection was used to downregulate XPOT expression in MDA-MB-468/231 cell lines followed by cell proliferation assessed via Cell Counting Kit-8 assays, meanwhile, BC cell migration and invasion capabilities were measured using Transwell test. Expression levels of CDK4/6 and key proteins in the PI3K/Akt/mTOR signaling pathway were assessed using Western blotting.
We found that XPOT was enriched in estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, larger tumor size, and cases with increased lymph node metastasis BC. XPOT was identified as a potential biomarker for the basal subtype of BC and a prognostic factor for the overall survival of patients with BC. Furthermore, XPOT promoted the proliferation and invasion of BC cells, likely through activation of the PI3K/AKT/mTOR signaling pathway, which in turn to upregulate cyclin D and CDK4/6 to drive tumor progression.
Our findings indicate that XPOT overexpression is associated with poor clinical characteristics and poor prognosis in BC, promoting disease progression by activating PI3K/AKT/mTOR pathway. These findings highlight XPOT as a potential therapeutic target in BC.
乳腺癌（BC）是女性中最常见的恶性肿瘤。核转运蛋白T（XPOT）是核转运蛋白β家族的成员，已被确定为多种癌症的预后生物标志物，但其在BC中的作用仍未得到充分了解。本研究旨在探讨XPOT在BC中的临床特征和分子机制。
基于来自癌症基因组图谱数据库（TCGA）的966例BC患者队列和来自国际乳腺癌分子分类联盟数据库的1904例患者进行回顾性RNA测序数据分析，以分析XPOT表达与BC临床病理特征之间的相关性。此外，使用小干扰RNA转染下调MDA-MB-468/231细胞系中XPOT的表达，随后通过细胞计数试剂盒-8检测评估细胞增殖，同时，使用Transwell试验测量BC细胞的迁移和侵袭能力。使用蛋白质印迹法评估PI3K/Akt/mTOR信号通路中CDK4/6和关键蛋白的表达水平。
我们发现XPOT在雌激素受体（ER）阴性、孕激素受体（PR）阴性、肿瘤体积较大以及淋巴结转移增加的BC病例中富集。XPOT被确定为BC基底亚型的潜在生物标志物和BC患者总生存的预后因素。此外，XPOT可能通过激活PI3K/AKT/mTOR信号通路促进BC细胞的增殖和侵袭，进而上调细胞周期蛋白D和CDK4/6以驱动肿瘤进展。
我们的研究结果表明，XPOT过表达与BC的不良临床特征和不良预后相关，通过激活PI3K/AKT/mTOR通路促进疾病进展。这些发现突出了XPOT作为BC潜在治疗靶点的地位。
