The role of Snail1 transcription factor in colorectal cancer progression and metastasis

M. Brzozowa, M. Michalski, G. Wyrobiec, A. Piecuch, Anna Dittfeld, M. Harabin-Słowińska, D. Boroń, R. Wojnicz
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引用次数: 32

Abstract

Snail1 is a zinc-finger transcription factor, which plays a role in colorectal cancer development by silencing E-cadherin expression and inducing epithelialmesenchymal transition (EMT). During EMT tumour cells acquire a mesenchymal phenotype that is responsible for their invasive activities. Consequently, Snail1 expression in colorectal cancer is usually associated with progression and metastasis. Some studies revealed that about 77% of colon cancer samples display Snail1 immunoreactivity both in activated fibroblasts and in carcinoma cells that have undergone EMT. Therefore, expression of this factor in the stroma may indicate how many cells possess the abilities to escape from the primary tumour mass, invade the basal lamina and colonise distant target organs. Blocking snail proteins activity has the potential to avert cancer cell metastasis by interfering with such cellular processes as remodelling of the actin cytoskeleton, migration and invasion, which are clearly associated with the aggressive phenotype of the disease. Moreover, the link between factors from the snail family and cancer stem cells suggests that inhibitory agents may also prove their potency as inhibitors of cancer recurrence.
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Snail1转录因子在结直肠癌进展和转移中的作用
Snail1是一种锌指转录因子,通过沉默E-cadherin表达和诱导上皮间质转化(epithelial - mesenchymal transition, EMT)在结直肠癌的发展中发挥作用。在EMT期间,肿瘤细胞获得负责其侵袭性活动的间充质表型。因此,Snail1在结直肠癌中的表达通常与进展和转移有关。一些研究表明,大约77%的结肠癌样本在活化的成纤维细胞和接受EMT的癌细胞中都显示出Snail1免疫反应性。因此,基质中该因子的表达可能表明有多少细胞具有逃离原发肿瘤块、侵入基底膜并定植远处靶器官的能力。阻断蜗牛蛋白活性有可能通过干扰肌动蛋白细胞骨架的重塑、迁移和侵袭等细胞过程来避免癌细胞转移,这些细胞过程显然与疾病的侵袭性表型相关。此外,来自蜗牛家族的因子和癌症干细胞之间的联系表明,抑制剂也可能证明它们作为癌症复发抑制剂的效力。
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