Snail regulates cell survival and inhibits cellular senescence in human metastatic prostate cancer cell lines
Snail regulates cell survival and inhibits cellular senescence in human metastatic prostate cancer cell lines
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DOI：
10.1007/s10565-010-9163-5
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发表时间：
2010-12-01
影响因子：
6.1
通讯作者：
Schulz, Wolfgang A.
中科院分区：
文献类型：
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作者：
Baygi, Modjtaba Emadi;Soheili, Zahra Soheila;Schulz, Wolfgang A.
上皮间质转化（EMT）被认为是肿瘤转移的重要环节。Snail是EMT的主要调节因子，最近被提出作为细胞存活因子和运动诱导剂。我们研究了Snail（SNAI 1）在前列腺癌细胞中的功能，通过短（21-mer）干扰RNA（siRNA）下调其表达，并测量对EMT标志物、细胞活力、死亡、细胞周期、衰老、附着和侵袭力的影响。定量RT-PCR检测结果显示，在8种前列腺癌细胞系中，前列腺癌细胞系LNCaP和PC-3的SNAI 1 mRNA表达量最高，而PC-3的表达量最低。长期敲除Snail诱导LNCaP和PC-3细胞数量严重下降，两种细胞系中caspase活性相应增强。此外，抑制Snail表达诱导LNCaP细胞衰老。SNAI 1-siRNA处理的细胞不能耐受从细胞外基质的脱离，这可能是由于整合素α 6的下调。E-cadherin、vimentin和fibronectin的表达也受到影响。PC-3细胞的侵袭性没有被Snail敲除显著降低。我们的数据表明，蜗牛主要作为一个生存因子和抑制剂的细胞衰老的前列腺癌细胞系。因此，我们认为Snail可以作为前列腺癌进展的早期驱动因素。
The epithelial-mesenchymal transition (EMT) is regarded as an important step in cancer metastasis. Snail, a master regulator of EMT, has been recently proposed to act additionally as a cell survival factor and inducer of motility. We have investigated the function of Snail (SNAI1) in prostate cancer cells by downregulating its expression via short (21-mer) interfering RNA (siRNA) and measuring the consequences on EMT markers, cell viability, death, cell cycle, senescence, attachment, and invasivity. Of eight carcinoma cell lines, the prostate carcinoma cell lines LNCaP and PC-3 showed the highest and moderate expression of SNAI1 mRNA, respectively, as measured by quantitative RT-PCR. Long-term knockdown of Snail induced a severe decline in cell numbers in LNCaP and PC-3 and caspase activity was accordingly enhanced in both cell lines. In addition, suppression of Snail expression induced senescence in LNCaP cells. SNAI1-siRNA-treated cells did not tolerate detachment from the extracellular matrix, probably due to downregulation of integrin alpha 6. Expression of E-cadherin, vimentin, and fibronectin was also affected. Invasiveness of PC-3 cells was not significantly diminished by Snail knockdown. Our data suggest that Snail acts primarily as a survival factor and inhibitor of cellular senescence in prostate cancer cell lines. We therefore propose that Snail can act as early driver of prostate cancer progression.