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牛磺酸减弱亚牛磺酸诱导的结直肠癌ERK/RSK信号通路进展。

Taurine Attenuates the Hypotaurine-Induced Progression of CRC ERK/RSK Signaling.

作者信息

Hou Xiaodan, Hu Junwei, Zhao Xinyu, Wei Qing, Zhao Rongping, Li Min, Li Qiong

机构信息

Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Suzhou Institute of Systems Medicine, Center of Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.

出版信息

Front Cell Dev Biol. 2021 Apr 15;9:631163. doi: 10.3389/fcell.2021.631163. eCollection 2021.

Abstract

Colorectal cancer (CRC) is one of the most common malignant tumors, and previous metabolomics work has demonstrated great promise in identifying specific small molecules of tumor phenotype. In the present study, we analyzed the metabolites of resected tissues through gas chromatography-mass spectrometry (GC-MS), and found that the concentration of taurine in CRC tissues diminished whereas the concentration of hypotaurine increased. The results demonstrated that taurine significantly suppressed cellular proliferation, metastasis, and colony formation whereas it induced apoptosis in CRC cells. Furthermore, taurine regulated the expression levels of epithelial mesenchymal transition (EMT)-associated genes in a dose-dependent manner. Taurine also alleviated hypotaurine-induced CRC progression, which was linked to the inhibition of the ERK/RSK-signaling pathway and diminution in intracellular hypotaurine. Taurine additionally attenuated hypotaurine-induced tumor growth and metastasis Patients with CRC exhibited lower levels of serum taurine, suggesting that taurine might be a promising biomarker reflecting a poor prognosis in CRC. Collectively, our results demonstrated that taurine-attenuated, hypotaurine-induced CRC progression provides a potential target for CRC therapy.

摘要

结直肠癌(CRC)是最常见的恶性肿瘤之一,先前的代谢组学研究已在识别肿瘤表型的特定小分子方面显示出巨大潜力。在本研究中,我们通过气相色谱 - 质谱联用(GC - MS)分析了切除组织的代谢物,发现CRC组织中牛磺酸浓度降低而次牛磺酸浓度升高。结果表明,牛磺酸显著抑制CRC细胞的增殖、转移和集落形成,同时诱导细胞凋亡。此外,牛磺酸以剂量依赖方式调节上皮 - 间质转化(EMT)相关基因的表达水平。牛磺酸还缓解了次牛磺酸诱导的CRC进展,这与抑制ERK/RSK信号通路和细胞内次牛磺酸减少有关。牛磺酸还减弱了次牛磺酸诱导的肿瘤生长和转移。CRC患者血清牛磺酸水平较低,提示牛磺酸可能是反映CRC预后不良的有前景的生物标志物。总体而言,我们的结果表明,牛磺酸减弱次牛磺酸诱导的CRC进展为CRC治疗提供了一个潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33c9/8083965/c78aab633d87/fcell-09-631163-g001.jpg

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