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GGCT通过上皮-间质转化促进结直肠癌的迁移和侵袭。

GGCT promotes colorectal cancer migration and invasion via epithelial-mesenchymal transition.

作者信息

Huang Qi, Zhou Yuanhang, Li Yue, Liao Zhiwei

机构信息

Department of General Surgery, Renhe Hospital, Shanghai 200431, P.R. China.

出版信息

Oncol Lett. 2020 Aug;20(2):1063-1070. doi: 10.3892/ol.2020.11692. Epub 2020 May 30.

Abstract

Colorectal cancer (CRC) is one of the most common malignancies, and the fourth most common cause of cancer-associated mortality globally. The epithelial to mesenchymal transition (EMT) serves an important function in metastatic dissemination and determines the aggressiveness of CRC. However, the regulatory mechanism of EMT in CRC has not yet been elucidated. γ-glutamylcyclotransferase (GGCT) is an important enzyme in glutathione metabolism and highly expressed in numerous forms of cancer, making it a promising therapeutic target. In the present study, GGCT was demonstrated to be highly expressed in CRC tissues, and patients with CRC with a higher expression of GGCT exhibited a worse prognosis compared with patients exhibiting a lower expression of GGCT. This result suggests that GGCT may serve as a novel prognostic marker for CRC. Furthermore, GGCT was indicated to promote CRC cell migration and invasion through regulating EMT-associated genes, including N-cadherin, Vimentin, snail family transcriptional repressor 2 and snail family transcriptional repressor 1. In conclusion, the present study provides novel insights into the mechanism governing CRC migration and invasion, and identified GGCT as a promising therapeutic target that may be used in the treatment of CRC.

摘要

结直肠癌(CRC)是最常见的恶性肿瘤之一,也是全球癌症相关死亡的第四大常见原因。上皮-间质转化(EMT)在转移扩散中起重要作用,并决定了CRC的侵袭性。然而,CRC中EMT的调控机制尚未阐明。γ-谷氨酰环转移酶(GGCT)是谷胱甘肽代谢中的一种重要酶,在多种癌症中高表达,使其成为一个有前景的治疗靶点。在本研究中,GGCT在CRC组织中高表达,与GGCT低表达的CRC患者相比,GGCT高表达的CRC患者预后更差。这一结果表明,GGCT可能作为CRC的一种新型预后标志物。此外,GGCT被表明通过调节与EMT相关的基因促进CRC细胞迁移和侵袭,这些基因包括N-钙黏蛋白、波形蛋白、蜗牛家族转录抑制因子2和蜗牛家族转录抑制因子1。总之,本研究为CRC迁移和侵袭的调控机制提供了新的见解,并确定GGCT是一种有前景的治疗靶点,可用于CRC的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dbd/7377102/52b5deb9955c/ol-20-02-1063-g00.jpg

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