Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, College of Life Science, Jilin University, Changchun 130012, China.
Vascular Biology Program, Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Int J Mol Sci. 2020 May 11;21(9):3385. doi: 10.3390/ijms21093385.
Mucin2 (Muc2) is the main component of the intestinal mucosal layer and is highly expressed in mucous colorectal cancer. Previous studies conducted by our lab found that the recombinant protein Amuc_1434 (expressed in prokaryote cell system, hereinafter termed Amuc_1434*), derived from , can degrade Muc2. Thus, the main objective of this study was to explore the effects of Amuc_1434* on LS174T in colorectal cancer cells expressing Muc2. Results from this study demonstrated that Amuc_1434* inhibited the proliferation of LS174T cells, which was related to its ability to degrade Muc2. Amuc_1434* also blocked the G0/G1 phase of the cell cycle of LS174T cells and upregulated the expression of tumor protein 53 (p53), which is a cell cycle-related protein. In addition, Amuc_1434* promoted apoptosis of LS174T cells and increased mitochondrial ROS levels in LS174T cells. The mitochondrial membrane potential of LS174T cells was also downregulated by Amuc_1434*. Amuc_1434* can activate the death receptor pathway and mitochondrial pathway of apoptosis by upregulating tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL). In conclusion, our study was the first to demonstrate that the protein Amuc_1434* derived from suppresses LS174T cell viability via TRAIL-mediated apoptosis pathway.
黏蛋白 2（Muc2）是肠黏膜层的主要成分，在黏液性结直肠癌中高度表达。本实验室之前的研究发现，来源于 的重组蛋白 Amuc_1434（在原核细胞系统中表达，以下称为 Amuc_1434*）可以降解 Muc2。因此，本研究的主要目的是探讨 Amuc_1434对表达 Muc2 的结直肠癌细胞 LS174T 的影响。研究结果表明，Amuc_1434抑制 LS174T 细胞的增殖，这与其降解 Muc2 的能力有关。Amuc_1434还阻断 LS174T 细胞的 G0/G1 期细胞周期，并上调肿瘤蛋白 53（p53）的表达，p53 是一种与细胞周期相关的蛋白。此外，Amuc_1434促进 LS174T 细胞凋亡，并增加 LS174T 细胞中线粒体 ROS 水平。Amuc_1434还下调 LS174T 细胞的线粒体膜电位。Amuc_1434可以通过上调肿瘤坏死因子相关凋亡诱导配体（TRAIL）激活凋亡的死亡受体途径和线粒体途径。总之，本研究首次证明来源于 的蛋白 Amuc_1434*通过 TRAIL 介导的凋亡途径抑制 LS174T 细胞活力。
