2. Academic Validation
  3. Cordycepin reprogramming lipid metabolism to block metastasis and EMT via ERO1A/mTOR/SREBP1 axis in cholangiocarcinoma

Cordycepin reprogramming lipid metabolism to block metastasis and EMT via ERO1A/mTOR/SREBP1 axis in cholangiocarcinoma

  • Life Sci. 2023 Apr 18;121698. doi: 10.1016/j.lfs.2023.121698.
Xuebing Zhou 1,  Chunyu Yang 1,  Yuan Li 1,  Dan Chen 1,  Tong Wang 1,  Tesi Liu 2,  Wendi Yan 3,  Zhaoxia Su 1,  Bosen Peng 1,  Xiangshan Ren 4
Affiliations

Affiliations

  • 1 Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, China.
  • 2 Otorhinolaryngology Institute at Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
  • 3 Department of Pathology of Jilin Cancer Hospital, Jilin, china.
  • 4 Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, China; Key Laboratory of Pathobiology, Yanbian University, State Ethnic Affairs Commission, Yanji, China. Electronic address: renxsh@ybu.edu.cn.
PMID: 37080351 DOI: 10.1016/j.lfs.2023.121698
Abstract

Cholangiocarcinoma (CCA) with a high malignancy is usually diagnosed as advanced and is prone to metastasis and leads to a poor prognosis. It is reported that cordycepin has anti-tumor effect. However, the molecular targets and mechanisms of cordycepin in inhibiting CCA metastasis remains unclear. In order to evaluate the therapeutic effect of cordycepin on CCA metastasis, experiments were conducted in vivo and in vitro. The results showed that cordycepin inhibited the migration and EMT progression of HuCCT1 and QBC939 cells. Cordycepin has a strong hypolipidemic effects, therefore, we examined its effect on lipid metabolism in CCA. Cordycepin inhibits SREBP1 mediated fatty acid synthesis through the Akt/mTOR signaling pathway. Meanwhile, cordycepin can reduce ERO1A expression in HuCCT1 and QBC939 cells. ERO1A plays a role in malignant tumors. ERO1A promotes migration and lipid metabolism of CCA cells through Akt/mTOR signaling pathway. In addition, cordycepin significantly inhibited the tumor metastasis and the serum levels of TG and T-CHO in mice. Taken together, we demonstrate that cordycepin mediated ERO1A/mTOR/SREBP1 axis inhibits lipid metabolism and metastasis in CCA cells in vitro and in vivo. These data suggest that cordycepin can be used as a novel drug for the clinical treatment of CCA and to improve the prognosis.

Keywords

Cholangiocarcinoma; Cordycepin; ERO1A; Lipid metabolism; Metastasis.

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