Tensin3 is a negative regulator of cell migration and all four Tensin family members are downregulated in human kidney cancer.
Tensin3 is a negative regulator of cell migration and all four Tensin family members are downregulated in human kidney cancer.
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Tensin3 是细胞迁移的负调节因子，所有四个 Tensin 家族成员在人肾癌中均下调。
DOI：
10.1371/journal.pone.0004350
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Hafizi S
中科院分区：
文献类型：
--
作者：
Martuszewska D;Ljungberg B;Johansson M;Landberg G;Oslakovic C;Dahlbäck B;Hafizi S
细胞内蛋白质的Tensin家族（Tensin 1、Tensin 2、Tensin 3和Tensin 4）被认为是细胞外基质和细胞骨架之间的连接，从而介导细胞形状和运动性的信号传导。张力蛋白表达的失调先前已涉及人类癌症。在此，我们首次评估了所有四种Tensin在人肾细胞癌（RCC）研究中的意义，并探讨了Tensin 3的生物学功能。Tensin 2和Tensin 3在mRNA和蛋白质水平上的表达在一组不同的人类癌细胞系中基本上不存在。定量RT-PCR分析显示所有四种Tensin基因的mRNA表达在人肾肿瘤中显著下调（相对于正常肾皮质降低50-100%; P<0.001）。Tensins mRNA表达与肿瘤分级呈负相关，与肿瘤大小无相关性。免疫组织化学分析显示，Tensin 3存在于正常人肾脏切片的肾小管上皮细胞的细胞质中，而在41%的肾脏肿瘤中表达较弱或不存在。肿瘤切片的一个子集显示出Tensin 3的优先质膜表达，这在透明细胞RCC患者中与较长的生存期相关。Tensin 3在HEK 293细胞中的稳定表达显著抑制细胞迁移和基质侵袭，这一功能独立于Tensin 3中假定的磷酸酶活性。相反，siRNA敲低人癌细胞中的内源性Tensin 3显著增加了它们的迁移。我们的研究结果表明，张力蛋白可能代表肾脏中一组新的转移抑制因子，其缺失会导致肿瘤细胞运动性增强并随之发生转移。此外，人肾脏中的肿瘤发生可通过张力蛋白的普遍下调来促进。因此，抗转移疗法可受益于恢复或保留原发性肿瘤中的张力蛋白表达。
The Tensin family of intracellular proteins (Tensin1, -2, -3 and -4) are thought to act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Dysregulation of Tensin expression has previously been implicated in human cancer. Here, we have for the first time evaluated the significance of all four Tensins in a study of human renal cell carcinoma (RCC), as well as probed the biological function of Tensin3. Expression of Tensin2 and Tensin3 at mRNA and protein levels was largely absent in a panel of diverse human cancer cell lines. Quantitative RT-PCR analysis revealed mRNA expression of all four Tensin genes to be significantly downregulated in human kidney tumors (50–100% reduction versus normal kidney cortex; P<0.001). Furthermore, the mRNA expressions of Tensins mostly correlated positively with each other and negatively with tumor grade, but not tumor size. Immunohistochemical analysis revealed Tensin3 to be present in the cytoplasm of tubular epithelium in normal human kidney sections, whilst expression was weaker or absent in 41% of kidney tumors. A subset of tumor sections showed a preferential plasma membrane expression of Tensin3, which in clear cell RCC patients was correlated with longer survival. Stable expression of Tensin3 in HEK 293 cells markedly inhibited both cell migration and matrix invasion, a function independent of putative phosphatase activity in Tensin3. Conversely, siRNA knockdown of endogenous Tensin3 in human cancer cells significantly increased their migration. Our findings indicate that the Tensins may represent a novel group of metastasis suppressors in the kidney, the loss of which leads to greater tumor cell motility and consequent metastasis. Moreover, tumorigenesis in the human kidney may be facilitated by a general downregulation of Tensins. Therefore, anti-metastatic therapies may benefit from restoring or preserving Tensin expression in primary tumors.
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影响因子：
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作者：
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通讯作者：
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通讯作者：
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