Willis Naomi D, Wilson Robert G, Hutchison Christopher J
School of Biological and Biomedical Sciences, Durham University, Durham, UK.
Biochem Soc Trans. 2008 Dec;36(Pt 6):1350-3. doi: 10.1042/BST0361350.
Abnormalities in the expression, distribution and structural organization of A-type lamins are most commonly associated with a spectrum of inherited disorders which predominantly affect mesenchymal lineages, collectively known as laminopathies. However, a new role for lamin A has been discovered in the progression of a common epithelial cancer. CRC (colorectal cancer) patients expressing lamin A/C in their tumour tissue were found to have a 2-fold greater risk of CRC-related mortality compared with patients with lamin A/C-negative tumours. Consequently, lamin A/C is a prognostic biomarker in CRC. In vitro studies suggest that lamin A is an upstream regulator of a pathway linking actin dynamics to loss of cell adhesion, leading to enhanced cell motility and consequently increased invasive potential within a tumour. The finding that lamin A is a putative colonic epithelial stem cell biomarker suggests that the poor outcome associated with lamin A/C-positive tumours may be reflective of a more stem-cell-like phenotype. The present review discusses the link between lamin A expression and tumour progression in one of the commonest causes of cancer-related death in the Western world.
A型核纤层蛋白在表达、分布和结构组织上的异常最常与一系列主要影响间充质谱系的遗传性疾病相关,这些疾病统称为核纤层蛋白病。然而,在一种常见上皮癌的进展过程中发现了核纤层蛋白A的新作用。与核纤层蛋白A/C阴性肿瘤患者相比,在肿瘤组织中表达核纤层蛋白A/C的结直肠癌(CRC)患者发生CRC相关死亡的风险高出2倍。因此,核纤层蛋白A/C是CRC的一种预后生物标志物。体外研究表明,核纤层蛋白A是一条将肌动蛋白动力学与细胞黏附丧失联系起来的信号通路的上游调节因子,导致细胞运动增强,进而增加肿瘤内的侵袭潜能。核纤层蛋白A是一种假定的结肠上皮干细胞生物标志物这一发现表明,与核纤层蛋白A/C阳性肿瘤相关的不良预后可能反映了一种更类似干细胞的表型。本综述讨论了在西方世界癌症相关死亡最常见原因之一中核纤层蛋白A表达与肿瘤进展之间的联系。