Department of Biomedical Sciences, Cooper Medical School of Rowan University, MEB 534, 401 South Broadway, Camden, NJ, 08103, USA.
Molecular and Cell Biology and Neuroscience Program, Rowan-Virtua School of Translational Biomedical Engineering and Sciences, Stratford, NJ, 08084, USA.
Sci Rep. 2024 Aug 28;14(1):19998. doi: 10.1038/s41598-024-70752-5.
During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer cells showed similar results. Supporting the clinical relevance of emerin reduction in cancer progression, our analysis of 192 breast cancer patient samples showed emerin expression inversely correlates with cancer invasiveness. We conclude emerin loss is an important driver of invasive transformation and has utility as a biomarker for tumor progression.
在转移过程中，癌细胞通过挤压穿过内皮细胞的非常小的间隙来穿越脉管系统。因此，转移性癌细胞的核必须变得更加柔韧，才能通过这些间隙。我们的实验室表明，侵袭性乳腺癌细胞的emerin 蛋白减少了 50%，导致核变小、变形，转移率高于非癌对照。因此，emerin 缺乏被预测会导致核顺应性、细胞迁移和转移增加。我们通过下调非侵袭性 MCF7 细胞中的 emerin 来验证这一假设，发现 emerin 敲低导致核变小、畸形，从而导致细胞迁移受阻增加。侵袭性乳腺癌细胞中的 emerin 减少也显示出类似的结果。支持 emerin 减少在癌症进展中的临床相关性，我们对 192 名乳腺癌患者样本的分析表明，emerin 的表达与癌症侵袭性呈负相关。我们得出结论，emerin 的缺失是侵袭性转化的重要驱动因素，并可用作肿瘤进展的生物标志物。
