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TMEM180 contributes to SW480 human colorectal cancer cell proliferation through intra-cellular metabolic pathways
Translational Oncology ( IF 5 ) Pub Date : 2021-07-28 , DOI: 10.1016/j.tranon.2021.101186
Takahiro Anzai 1 , Shinji Saijou 2 , Yoshitsugu Ohnuki 3 , Hiroshi Kurosawa 3 , Masahiro Yasunaga 1 , Yasuhiro Matsumura 4
Affiliation  

TMEM180, a novel colon cancer–specific protein with a 12-transmembrane topology, is upregulated at low oxygen. Previously, we established a humanized monoclonal antibody against TMEM180 aimed at clinical trials. Prior to such trials, it is necessary to clarify the function of TMEM180 in cancer. To compare SW480 human colon cancer cells and their TMEM180-knockdown derivatives, we analyzed proliferation and oxygen consumption, and also performed phosphorylation proteomics, metabolomics, and next-generation sequencing (NGS). The preliminary results revealed that TMEM180 appeared to promote the growth of colon cancer but had almost no effect on oxygen consumption or expression of phosphorylated proteins. By contrast, glycolysis differed dramatically between SW480 and TMEM180-knockdown cells. The NGS analysis revealed that TMEM180 promotes enzyme expression in nitric oxide (NO) synthesis system, suggesting that it promotes glucose and glutamine metabolism, thereby contributing to cancer growth. Overall, the results of this study warrant further basic studies of TMEM180 molecule.



中文翻译:

TMEM180 通过细胞内代谢途径促进 SW480 人结肠直肠癌细胞增殖

TMEM180 是一种新型结肠癌特异性蛋白,具有 12 跨膜拓扑结构,在低氧条件下上调。此前,我们针对TMEM180建立了针对临床试验的人源化单克隆抗体。在进行此类试验之前,有必要阐明 TMEM180 在癌症中的功能。为了比较 SW480 人类结肠癌细胞及其TMEM180 敲低衍生物,我们分析了增殖和耗氧量,还进行了磷酸化蛋白质组学、代谢组学和下一代测序 (NGS)。初步结果显示,TMEM180 似乎促进了结肠癌的生长,但对耗氧量或磷酸化蛋白的表达几乎没有影响。相比之下,SW480 和TMEM180之间的糖酵解差异很大- 击倒细胞。NGS 分析显示 TMEM180 促进一氧化氮 (NO) 合成系统中的酶表达,表明它促进葡萄糖和谷氨酰胺代谢,从而促进癌症生长。总的来说,这项研究的结果值得对 TMEM180 分子进行进一步的基础研究。

更新日期:2021-07-28
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