Expression of ALG3 in Hepatocellular Carcinoma and Its Clinical Implication

Zhao, Zhen; Zheng, Zehao; Huang, Jianfeng; Wang, Jianxi; Peng, Tianyi; Lin, Ye; Jian, Zhixiang

doi:10.3389/fmolb.2022.816102

Cited by 4 publications

(1 citation statement)

References 49 publications

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“…There are several glycosyltransferases that also play an important role in cancer biology and are suggested as potential therapeutic targets. ALG3 (Alpha-1,3-Mannosyltransferase) was proved to be significantly upregulated in hepatocellular carcinoma, and its inhibition impeded the tumoral proliferation [44], while it also holds promise as a potential marker for increased sensitivity to radiation therapy, serving as an effective target to reduce radioresistance by modulating the glycosylation of TGFBR2 in breast cancer [45]. In addition, studies have shown that suppression of GALNT6 (pp-GalNAc-T6) decreases the oncofetal fibronectin expression but also effectively reverses the multidrug resistance (MDR) phenotype, as evidenced by heightened sensitivity to various types of anticancer medications [46].…”

Section: Targeting Glycosylationmentioning

confidence: 99%

Golgi’s Role in the Development of Possible New Therapies in Cancer

Vlad,

Dumitrascu,

Dumitrascu

2023

Cells

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The Golgi apparatus is an important organelle found in most eukaryotic cells. It plays a vital role in the processing and sorting of proteins, lipids and other cellular components for delivery to their appropriate destinations within the cell or for secretion outside of the cell. The Golgi complex also plays a role in the regulation of protein trafficking, secretion and post-translational modifications, which are significant in the development and progression of cancer. Abnormalities in this organelle have been observed in various types of cancer, although research into chemotherapies that target the Golgi apparatus is still in its early stages. There are a few promising approaches that are being investigated: (1) Targeting the stimulator of interferon genes protein: The STING pathway senses cytosolic DNA and activates several signaling events. It is regulated by numerous post-translational modifications and relies heavily on vesicular trafficking. Based on some observations which state that a decreased STING expression is present in some cancer cells, agonists for the STING pathway have been developed and are currently being tested in clinical trials, showing encouraging results. (2) Targeting glycosylation: Altered glycosylation, which refers to changes in the carbohydrate molecules that are attached to proteins and lipids in cells, is a common feature of cancer cells, and there are several methods that thwart this process. For example, some inhibitors of glycosylation enzymes have been shown to reduce tumor growth and metastasis in preclinical models of cancer. (3) Targeting Golgi trafficking: The Golgi apparatus is responsible for the sorting and trafficking of proteins within the cell, and disrupting this process may be a potential therapeutic approach for cancer. The unconventional protein secretion is a process that occurs in response to stress and does not require the involvement of the Golgi organelles. P53 is the most frequently altered gene in cancer, dysregulating the normal cellular response to DNA damage. The mutant p53 drives indirectly the upregulation of the Golgi reassembly-stacking protein 55kDa (GRASP55). Through the inhibition of this protein in preclinical models, the reduction of the tumoral growth and metastatic capacity have been obtained successfully. This review supports the hypothesis that the Golgi apparatus may be the target of cytostatic treatment, considering its role in the molecular mechanisms of the neoplastic cells.

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Section: Targeting Glycosylationmentioning

confidence: 99%