Mucin-type O-glycosylation is one of the most common post-translational modifications in proteins, capable of altering protein conformation and biological functions. It plays a crucial role in biological processes such as cell signaling, cell adhesion, and immune responses. Polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), as the initiating enzyme of mucin-type O-glycosylation, is of paramount importance in maintaining the homeostasis of human cells and tissues. Dysfunction of GALNT3 has been found to play a role in various diseases, such as calcium-phosphorus metabolism disorders and atherosclerosis. Additionally, GALNT3 is abnormally expressed in several types of tumors, including colorectal cancer, lung cancer, and ovarian cancer. Its expression is associated with the clinical pathological features of patients and poor prognosis, making it a potential biomarker for early tumor diagnosis and prognosis evaluation. Further research shows that GALNT3 can both regulate glycosylation levels to reduce adhesion between tumor cells and activate multiple metabolism-related pathways, promoting tumor cell invasion and metastasis. This review summarizes the role of GALNT3 in the development of malignant tumors and discusses the prospects and challenges of developing anti-tumor drugs targeting GALNT3.
GAO Yixuan, ZHANG Yichi, DAI Luyan, MA Jiao. Research progress of GALNT3 as a potential tumor molecular marker and drug target. Journal of Shanghai Jiao Tong University (Medical Science)[J], 2024, 44(11): 1460-1465 doi:10.3969/j.issn.1674-8115.2024.11.014
在GALNT家族成员中，GALNT3参与多种生理过程，并且已发现其表达异常与人类癌症进展相关，如结肠癌、肺癌、胆囊癌、前列腺癌、胰腺癌等［12-14］。但相比GALNT家族中的其他成员，目前对GALNT3在肿瘤中的研究相对较少，并且也没有综述系统归纳过GALNT3与肿瘤发生发展的关系。而本课题组近期发现，GALNT3在弥漫性大B细胞淋巴瘤（diffuse large B cell lymphoma，DLBCL）中高表达，并且与DLBCL的预后密切相关，推测GALNT3不仅可以在实体瘤中发挥作用，也与血液肿瘤的发生发展有关。该文综述了GALNT3在人体中主要发挥的生理功能，重点讨论了该分子与多种癌症预后的关系，以及影响肿瘤细胞增殖、侵袭和转移的分子机制，并关注了GALNT3在DLBCL预后中发挥的作用。最后，该文介绍了目前靶向GALNT3的抗肿瘤药物研究，同时针对靶向糖基化在肿瘤治疗中的前景与挑战进行了探讨，并提出了未来新药研发的可行方向，以期为多种癌症的临床治疗提供更有效的策略和手段。
Note： The orange part represents the N-terminal cytoplasm tail, the purple part represents the transmembrane domain, the blue part is the stem region, the green part is the catalytic domain, the cyan part is the linker region, the red part represents the lectin domain, and the grey part is the C-terminal residue. The figure was prepared using PyMOL software.
Fig 1
Schematic diagram of structural conformation of GALNT3 protein
GAO Yixuan, ZHANG Yichi and DAI Luyan were responsible for writing and revision of the paper; MA Jiao was responsible for guiding article writing and participated in paper revision. All the authors have read the final manuscript and agreed to the submission.
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所有作者声明不存在利益冲突。
COMPETING INTERESTS
All the authors disclose no relevant conflict of interests.
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... 在GALNT家族成员中，GALNT3参与多种生理过程，并且已发现其表达异常与人类癌症进展相关，如结肠癌、肺癌、胆囊癌、前列腺癌、胰腺癌等［12-14］.但相比GALNT家族中的其他成员，目前对GALNT3在肿瘤中的研究相对较少，并且也没有综述系统归纳过GALNT3与肿瘤发生发展的关系.而本课题组近期发现，GALNT3在弥漫性大B细胞淋巴瘤（diffuse large B cell lymphoma，DLBCL）中高表达，并且与DLBCL的预后密切相关，推测GALNT3不仅可以在实体瘤中发挥作用，也与血液肿瘤的发生发展有关.该文综述了GALNT3在人体中主要发挥的生理功能，重点讨论了该分子与多种癌症预后的关系，以及影响肿瘤细胞增殖、侵袭和转移的分子机制，并关注了GALNT3在DLBCL预后中发挥的作用.最后，该文介绍了目前靶向GALNT3的抗肿瘤药物研究，同时针对靶向糖基化在肿瘤治疗中的前景与挑战进行了探讨，并提出了未来新药研发的可行方向，以期为多种癌症的临床治疗提供更有效的策略和手段. ...
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... 在GALNT家族成员中，GALNT3参与多种生理过程，并且已发现其表达异常与人类癌症进展相关，如结肠癌、肺癌、胆囊癌、前列腺癌、胰腺癌等［12-14］.但相比GALNT家族中的其他成员，目前对GALNT3在肿瘤中的研究相对较少，并且也没有综述系统归纳过GALNT3与肿瘤发生发展的关系.而本课题组近期发现，GALNT3在弥漫性大B细胞淋巴瘤（diffuse large B cell lymphoma，DLBCL）中高表达，并且与DLBCL的预后密切相关，推测GALNT3不仅可以在实体瘤中发挥作用，也与血液肿瘤的发生发展有关.该文综述了GALNT3在人体中主要发挥的生理功能，重点讨论了该分子与多种癌症预后的关系，以及影响肿瘤细胞增殖、侵袭和转移的分子机制，并关注了GALNT3在DLBCL预后中发挥的作用.最后，该文介绍了目前靶向GALNT3的抗肿瘤药物研究，同时针对靶向糖基化在肿瘤治疗中的前景与挑战进行了探讨，并提出了未来新药研发的可行方向，以期为多种癌症的临床治疗提供更有效的策略和手段. ...
