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GLDC promotes colorectal cancer metastasis through epithelial–mesenchymal transition mediated by Hippo signaling pathway

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Abstract

Cancer metastasis remains a major cause of death in cancer patients, and epithelial–mesenchymal transition (EMT) plays a decisive role in cancer metastasis. Recently, abnormal expression of Glycine Decarboxylase (GLDC) has been demonstrated in tumor progression, and GLDC is up-regulated in cancers, such as lung, prostate, bladder, and cervical cancers. However, the exact role of GLDC in colorectal cancer (CRC) progression remains to be elucidated. The aim of our study was to explore the role of GLDC in CRC metastasis. The GSE75117 database was used to investigate GLDC expression in tumor center and invasive front tissues and we found that GLDC expression levels were higher in the invasive front tissue. GLDC expression levels were negatively correlated with the prognosis of CRC patients. In vitro studies have showed that GLDC can promote invasion and migration of CRC cells by inhibiting the Hippo signaling pathway and regulating the EMT process. Blocking the Hippo signaling pathway with Verteporfin reduced the effect of GLDC on CRC metastasis. In vivo metastasis assays further confirmed that tail vein injection of GLDC+/+ cells induced more lung metastasis, compared to normal CRC cells. The results of this study suggest that GLDC promotes EMT through the Hippo signaling pathway, providing a new therapeutic target for CRC metastasis.

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Funding

This work was supported by the National Natural Science Foundation of China (grant numbers 82122075; 82074232; 82030118; 82004131; 81830120), Shanghai Frontier Research Base of Disease and Syndrome Biology of Inflammatory Cancer Trans-formation (2021KJ03-12), “Shu Guang” project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (21SG43), Three-year Plan Project of Shanghai Traditional Chinese Medicine(ZY(2021–2023)-0208), Clinical Research Plan of SHDC (SHDC2020CR4043), and Shanghai Youth Talent Support Program.

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  1. Hao Yu and Xueqing Hu have contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Hao Yu, Xueqing Hu, Yingru Zhang, Jiajia Wang, Zhongya Ni, Yan Wang & Huirong Zhu

  2. Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Xueqing Hu, Zhongya Ni & Yan Wang

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  1. Hao Yu
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  6. Yan Wang
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Contributions

HY and XH conceived and designed the study. HY and JW analyzed the data. HY and YZ drafted the paper. XH, YW, and HZ revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yan Wang or Huirong Zhu.

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All animal experimental studies have been approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (PZSHUTCM210913009).

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Yu, H., Hu, X., Zhang, Y. et al. GLDC promotes colorectal cancer metastasis through epithelial–mesenchymal transition mediated by Hippo signaling pathway. Med Oncol 40, 293 (2023). https://doi.org/10.1007/s12032-023-02076-9

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