间皮瘤细胞恶变:整合素α7缺失促进细胞迁移并导致患者临床预后不良。
Mesothelioma cells breaking bad: loss of integrin α7 promotes cell motility and poor clinical outcomes in patients.
作者信息
Burkin Dean J, Fontelonga Tatiana M
机构信息
Department of Pharmacology, Center for Molecular Medicine, University of Nevada School of Medicine, 1664 N Virginia Avenue, Reno, NV, 89557, USA.
出版信息
J Pathol. 2015 Nov;237(3):282-4. doi: 10.1002/path.4587. Epub 2015 Aug 26.
Mesothelioma is a disease of pleural cells lining the lungs which is often caused by exposure to asbestos. The molecular mechanism(s) that regulate the transformation of pleural mesothelioma cells to a migratory and malignant phenotype are unclear. In recent work published in this journal, Laszlo et al performed a set of elegant experiments to identify a key molecular mechanism that may explain the aggressive nature of this disease. Using patient-derived mesothelioma cells with high versus low migratory activity, the authors conducted a genome-wide expression analysis. They identified a significant reduction in ITGA7 expression only in highly migratory malignant pleural mesothelioma cells and showed that loss of ITGA7 expression was associated with methylation of the promoter. Forced expression of integrin α7 reversed the migratory phenotype of these cells. Finally, the authors identified a strong correlation between ITGA7 expression and patient survival. Together, these results identify expression of integrin α7 as a molecular mechanism for the aggressive migratory transformation of mesothelioma and identify a potentially novel diagnostic and therapeutic target.
间皮瘤是一种发生于肺脏表面胸膜细胞的疾病,通常由接触石棉所致。调节胸膜间皮瘤细胞转变为迁移性和恶性表型的分子机制尚不清楚。在近期发表于本杂志的研究中,拉兹洛等人开展了一系列精妙的实验,以确定一种可能解释该疾病侵袭性本质的关键分子机制。作者使用具有高迁移活性和低迁移活性的患者来源间皮瘤细胞,进行了全基因组表达分析。他们发现仅在高迁移性恶性胸膜间皮瘤细胞中整合素α7(ITGA7)表达显著降低,并表明ITGA7表达缺失与启动子甲基化有关。强制表达整合素α7可逆转这些细胞的迁移表型。最后,作者发现ITGA7表达与患者生存率之间存在强相关性。这些结果共同确定整合素α7的表达是间皮瘤侵袭性迁移转变的分子机制,并确定了一个潜在的新型诊断和治疗靶点。