MUC16 C-terminal binding with ALDOC disrupts the ability of ALDOC to sense glucose and promotes gallbladder carcinoma growth
MUC16 C-terminal binding with ALDOC disrupts the ability of ALDOC to sense glucose and promotes gallbladder carcinoma growth
复制标题
MUC16 C 末端与 ALDOC 结合破坏了 ALDOC 感知葡萄糖的能力并促进胆囊癌生长
DOI：
10.1016/j.yexcr.2020.112118
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发表时间：
2020-09-01
影响因子：
3.7
通讯作者：
Liu, Han
中科院分区：
文献类型：
--
作者：
Fan, Kun;Wang, Jiwen;Liu, Han
MUC16c末端（MUC16c）水平与肿瘤血清CA-125水平相关，然而，其在胆囊癌（GBC）中的作用尚不清楚。在本研究中，我们发现MUC16c促进葡萄糖摄取和糖酵解，促进GBC细胞增殖。质谱分析表明MUC16c可以与醛缩酶结合。ALDOC mRNA和蛋白在GBC肿瘤中过表达。免疫组化结果也显示。GBC肿瘤组织中ALDOC和MUC16c水平高于肿瘤周围组织。我们发现MUC16c与ALDOC结合可促进ALDOC蛋白的稳定性，破坏ALDOC感知葡萄糖缺乏的能力，激活AMPK通路，增加GBC细胞的增殖。ALDOC敲低显著抑制MUC16c诱导的葡萄糖摄取和糖酵解。我们的研究确定了MUC16c促进GBC细胞糖酵解和增殖的重要作用，揭示了ca -125相关肿瘤重代谢负担在GBC中的潜在机制。
The MUC16 C-terminal (MUC16c) level is associated with tumor serum CA-125 levels, however, the roles remain unclear in gallbladder carcinoma (GBC). In this study, we found that MUC16c promoted glucose uptake and glycolysis for GBC cell proliferation. Mass spectrometry analysis suggested that MUC16c could combine with aldolase. The ALDOC mRNA and protein are overexpressed in GBC tumors. The IHC results also showed the consistent up-regulation of.ALDOC and MUC16c level in GBC tumor tissues than in peritumor tissues. We determined that MUC16c combining with ALDOC promoted ALDOC protein stability and disrupted the ability of ALDOC sensing glucose deficiency, which activated AMPK pathway and increased GBC cell proliferation. ALDOC knockdown significantly inhibited the glucose uptake and glycolysis induced by MUC16c. Our study established important roles of MUC16c promoting GBC cell glycolysis and proliferation and revealed the underlying mechanism of CA-125-related heavy tumor metabolic burden in GBC.