2. Academic Validation
  3. ST6GALNAC4 promotes hepatocellular carcinogenesis by inducing abnormal glycosylation

ST6GALNAC4 promotes hepatocellular carcinogenesis by inducing abnormal glycosylation

  • J Transl Med. 2023 Jun 29;21(1):420. doi: 10.1186/s12967-023-04191-7.
Da Man # 1 2 3 4,  Yifan Jiang # 1 2 4,  Deguo Zhang 1 2 3 4,  Jingjing Wu 5,  Bo Ding 1 3 4,  Hanqing Liu 1 3 4,  Guangming Xu 1 3 4,  Jiahua Lu 1 3 4,  Junnan Ru 1 3 4,  Rongliang Tong 1 2 3 4,  Shusheng Zheng 1 3 4,  Diyu Chen 6 7 8 9,  Jian Wu 10 11 12 13
Affiliations

Affiliations

  • 1 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China.
  • 2 NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang, China.
  • 3 Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, 310003, Zhejiang, China.
  • 4 Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, 310003, Zhejiang, China.
  • 5 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 6 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China. [email protected].
  • 7 NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang, China. [email protected].
  • 8 Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, 310003, Zhejiang, China. [email protected].
  • 9 Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, 310003, Zhejiang, China. [email protected].
  • 10 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China. [email protected].
  • 11 NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang, China. [email protected].
  • 12 Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, 310003, Zhejiang, China. [email protected].
  • 13 Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, 310003, Zhejiang, China. [email protected].
  • # Contributed equally.
PMID: 37381011 DOI: 10.1186/s12967-023-04191-7
Abstract

Hepatocellular carcinoma (HCC) is one of the most lethal tumor types worldwide. Glycosylation has shown promise in the study of tumor mechanisms and treatment. The glycosylation status of HCC and the underlying molecular mechanisms are still not fully elucidated. Using bioinformatic analysis we obtained a more comprehensive characterization of glycosylation of HCC. Our analysis presented that high glycosylation levels might correlate with tumor progression and poor prognosis. Subsequent Experiments identified key molecular mechanisms for ST6GALNAC4 promoting malignant progression by inducing abnormal glycosylation. We confirmed the contribution of ST6GALNAC4 to proliferation, migration, and invasion in vitro and in vivo. Mechanistic studies revealed that ST6GALNAC4 may be induced abnormal TGFBR2 glycosylation, resulting in the higher protein levels of TGFBR2 and TGF[Formula: see text] pathway increased activation. Our study also provided a further understand of immunosuppressive function of ST6GALNAC4 through T antigen-galectin3+ TAMs axis. This study has provided one such possibility that galectin3 inhibitors might be an acceptable treatment choice for HCC patients with high T antigen expression.

Keywords

Galectin3; Glycosylation; Hepatocellular carcinoma; Immunosuppressive; ST6GALNAC4.

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