2. Academic Validation
  3. 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

  • Exp Cell Res. 2020 Sep 1;394(1):112118. doi: 10.1016/j.yexcr.2020.112118.
Kun Fan 1,  Jiwen Wang 1,  Wentao Sun 1,  Sheng Shen 1,  Xiaojian Ni 1,  Zijun Gong 1,  Bohao Zheng 1,  Zhihui Gao 1,  Xiaoling Ni 1,  Tao Suo 2,  Houbao Liu 3,  Han Liu 4
Affiliations

Affiliations

  • 1 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Biliary Tract Disease Center of Zhongshan Hospital, Fudan University, Shanghai, China; Biliary Tract Disease Institute, Fudan University, Shanghai, China.
  • 2 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Biliary Tract Disease Center of Zhongshan Hospital, Fudan University, Shanghai, China; Biliary Tract Disease Institute, Fudan University, Shanghai, China. Electronic address: suo.tao@zs-hospital.sh.cn.
  • 3 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Biliary Tract Disease Center of Zhongshan Hospital, Fudan University, Shanghai, China; Biliary Tract Disease Institute, Fudan University, Shanghai, China. Electronic address: liu.houbao@zs-hospital.sh.cn.
  • 4 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Biliary Tract Disease Center of Zhongshan Hospital, Fudan University, Shanghai, China; Biliary Tract Disease Institute, Fudan University, Shanghai, China. Electronic address: liu.han@zs-hospital.sh.cn.
PMID: 32502493 DOI: 10.1016/j.yexcr.2020.112118
Abstract

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.

Keywords

ALDOC; AMPK pathway; Gallbladder carcinoma; Glycolysis; MUC16c.

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