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首页> 外文期刊>Journal of Cellular Physiology >Thrombin induces expression of twist and cell motility via the hypoxia-inducible factor-1alpha translational pathway in colorectal cancer cells.
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Thrombin induces expression of twist and cell motility via the hypoxia-inducible factor-1alpha translational pathway in colorectal cancer cells.

机译：凝血酶诱导的表达和细胞通过低氧诱导factor-1alpha能动性在结直肠癌细胞转化途径。

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Deep vein thrombosis associated with advanced cancer is known as Trousseau's syndrome. We hypothesized that thrombin, an activator of protease-activated receptor (PAR)-1 and PAR-4 contributes to tumor metastasis. In this study, we demonstrated that thrombin and the PAR-1 activating peptide (AP) SFLLRN, but not the PAR-4 AP GYPGKF, induced HIF-1alpha activities, protein expression, and cell motility in colorectal cancer cells, and these actions were significantly inhibited by the PAR-1 antagonist SCH79797. Moreover, thrombin-induced HIF-1alpha activity and cell motility were blocked by inhibiting important mediators of signaling transduction, including the ERK, PI3K, and mTOR pathways. These results showed that thrombin induced HIF-1alpha protein expression through PAR-1 and HIF-1alpha translational de novo protein synthesis. Twist can regulate epithelial-mesenchymal transition (EMT) and increase tumor metastasis. However, we observed that thrombin-induced HIF-1alpha increased Twist mRNA and its protein level was mediated by the modulation of PAR-1 activation and the HIF-1alpha translational pathway. In addition, Twist could increase N-cadherin but not E-cadherin to promote tumor metastasis. Overexpression of dominant-negative HIF-1alpha reversed thrombin-mediated Twist and Twist-induced N-cadherin expression. Moreover, siTwist inhibited Twist-induced N-cadherin and Thrombin-induced cell motility. In conclusion, our study showed that thrombin-induced HIF-1alpha upregulated Twist at the transcriptional level to enhance cell motility. These findings show that thrombin upregulates Twist via HIF-1alpha to make tumor cells malignant and also establish a link between the coagulation disorder and cancer metastasis.
机译：深静脉血栓形成与先进癌症被认为是嫁妆的综合症。推测,凝血酶的活化剂protease-activated受体(PAR) 1和4杆导致肿瘤转移。我们表明,凝血酶和PAR-1激活肽(美联社)SFLLRN,但不是4杆美联社GYPGKF、诱导HIF-1alpha活动、蛋白质表达式,并在大肠癌细胞活性癌症细胞,这些行动显著抑制PAR-1拮抗剂SCH79797。活动和细胞活性被封锁了抑制信号的重要介质转导,包括ERK、PI3K和mTOR通路。诱导HIF-1alpha蛋白表达PAR-1和HIF-1alpha平动新创蛋白质合成。epithelial-mesenchymal (EMT)和过渡增加肿瘤转移。, thrombin-induced HIF-1alpha增加转折信使rna及其介导的蛋白质水平调制PAR-1激活和HIF-1alpha转化途径。增加N-cadherin但不是促进钙粘蛋白肿瘤的转移。显性负HIF-1alpha逆转thrombin-mediated扭曲和Twist-inducedN-cadherin表达式。抑制Twist-induced N-cadherin和Thrombin-induced细胞的能动性。我们的研究表明,thrombin-induced HIF-1alpha在转录水平调节扭曲增强细胞的能动性。凝血酶通过HIF-1alpha上调扭曲肿瘤细胞恶性也建立一个链接凝血障碍和癌症之间转移。

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