LNK expression, subcellular localisation and survival associations in breast, cervical and colorectal cancer.

0 MEDICINE, RESEARCH & EXPERIMENTAL
Jessica C Mantilla-Ollarves, Alejandro Sánchez-Carballido, Alejandro Ordaz-Ramos, Cecilia Aguilar, Miguel Tapia-Rodríguez, Liliana Cortés-Ballinas, Laura Velázquez, Leticia Rocha-Zavaleta
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Abstract

The role of lymphocyte adaptor protein (LNK) in breast, cervical and colorectal cancer remains incompletely characterised. We examined LNK expression, subcellular localisation and associations with survival across these cancers. Gene Expression Profiling Interactive Analysis and cBioPortal were used to assess LNK messenger ribonucleic acid (mRNA) expression, while Kaplan-Meier Plotter was used for exploratory survival analyses. Western blotting and quantitative confocal immunofluorescence assessed protein expression and localisation in 12 cancer cell lines and three non-tumoural controls. LNK mRNA expression varied among tumour subtypes and was significantly lower in cervical tumours than in adjacent normal tissue. Higher expression was associated with longer overall and recurrence-free survival in triple-negative breast cancer but shorter survival for both endpoints in colorectal cancer; no significant associations were observed in cervical cancer. LNK was detected in the nucleus and cytoplasm of all cancer cell lines. Significant nuclear predominance was observed in one of four triple-negative breast cancer cell lines and three of four cervical cancer cell lines, whereas their non-tumoural controls showed cytoplasmic predominance. Colorectal cancer cell lines displayed heterogeneous subcellular distributions. These exploratory findings suggest cancer type-specific associations between LNK expression and survival that require independent validation, while nuclear localisation warrants investigation of potential nuclear functions.

LNK在乳腺癌、宫颈癌和结直肠癌中的表达、亚细胞定位和生存相关性
淋巴细胞适配蛋白(LNK)在乳腺癌、宫颈癌和结直肠癌中的作用尚未完全确定。我们研究了LNK的表达、亚细胞定位以及与这些癌症存活的关系。使用基因表达谱交互分析和cBioPortal评估LNK信使核糖核酸(mRNA)表达,使用Kaplan-Meier Plotter进行探索性生存分析。Western blotting和定量共聚焦免疫荧光评估了12种癌细胞系和3种非肿瘤对照的蛋白质表达和定位。LNK mRNA的表达在不同的肿瘤亚型中存在差异,在宫颈肿瘤中的表达明显低于邻近正常组织。在三阴性乳腺癌中,高表达与较长的总生存期和无复发生存期相关,但在结直肠癌中,这两个终点的生存期都较短;在子宫颈癌中未观察到明显的关联。所有癌细胞的细胞核和细胞质中均检测到LNK。在四种三阴性乳腺癌细胞系中的一种和四种宫颈癌细胞系中的三种中观察到显著的核优势,而它们的非肿瘤对照则表现出细胞质优势。结直肠癌细胞系亚细胞分布呈异质性。这些探索性发现表明,LNK表达与生存之间的癌症类型特异性关联需要独立验证,而核定位需要对潜在的核功能进行研究。
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1.10
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