Blockage of O-linked GlcNAcylation induces AMPK-dependent autophagy in bladder cancer cells

Jin, Lu; Yuan, Feng; Dai, Guangcheng; Yao, Qing; Han, Xiaowei; Wang, Lixia; Xue, Boxin; Shan, Yuxi; Liu, Xiaolong

doi:10.1186/s11658-020-00208-x

Cited by 29 publications

(22 citation statements)

References 35 publications

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“…According to Jin et al. 67 a negative correlation existed between AMPK activation and the O-GlcNAcylation of AMPK: the phosphorylation of AMPK decreased with its O-GlcNAcylation.…”

Section: Cell Death Effects Of Autophagy On Bladder Cancer Cellsmentioning

confidence: 99%

Contrast effects of autophagy in the treatment of bladder cancer

Konac

Kurman

Baltacı

2020

Exp Biol Med (Maywood)

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Bladder cancer is a disease that negatively affects patients’ quality of life, but treatment options have remained unchanged for a long time. Although promising results have been achieved with current bladder cancer treatments, cancer recurrence, progression, and therapy resistance are the most severe problems preventing the efficiency of bladder cancer treatments. Autophagy refers to an evolutionarily conserved catabolic process in which proteins, damaged organelles, and cytoplasmic components are degraded by lysosomal enzymes. Autophagy regulates the therapeutic response to the chemotherapy drugs, thus determining the effect of therapy on cancer cells. Autophagy is a stress-induced cell survival mechanism and its excessive stimulation can cause resistance of tumor cells to therapeutic agents. Depending on the conditions, an increase in autophagy may cause treatment resistance or autophagic cell death, and it is related to important anti-cancer mechanisms, such as apoptosis. Therefore, understanding the roles of autophagy under different conditions is important for designing effective anti-cancer agents. The dual role of autophagy in cancer has attracted considerable attention in respect of bladder cancer treatment. In this review, we summarize the basic characteristics of autophagy, including its mechanisms, regulation, and functions, and we present examples from current studies concerning the dual role of autophagy in bladder cancer progression and therapy. Impact statement Autophagy acts as an intracellular recycling system. Infection and mitochondrial damage, maintaining cellular homeostasis, orchestrating nutrient stress, hypoxia, and oxidative stress are some of the physiological roles associated with autophagy. Autophagy has also context-dependent roles in cancer. Autophagy has a significant impact on tumor initiation and promotion, with both tumor-suppressive and tumor-promoting roles. Unfortunately, conventional systemic chemotherapy for cancer therapy has been reported to have primary limitations such as chemo-resistance of targeted cells. The cytoprotective role of autophagy has been postulated as one of the causes of this resistance. Hence, combination therapy using autophagy inhibitors has recently started to emerge as a noteworthy strategy in the treatment of cancer. Therefore, targeting the autophagy pathways may be a potential therapeutic strategy for addressing cancer progression or therapy resistance in the near future. This review will provide a novel insight to understanding the paradoxical roles of autophagy in tumor suppression and tumor promotion.

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“…According to Jin et al. 67 a negative correlation existed between AMPK activation and the O-GlcNAcylation of AMPK: the phosphorylation of AMPK decreased with its O-GlcNAcylation.…”

Section: Cell Death Effects Of Autophagy On Bladder Cancer Cellsmentioning

confidence: 99%

Contrast effects of autophagy in the treatment of bladder cancer

Konac

Kurman

Baltacı

2020

Exp Biol Med (Maywood)

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“…More in-depth research results confirmed the correlation between the OGT protein level and tumor metastatic progression in prostate cancer cells (32). In addition, downregulation of O-GlcNAcylation induced by OGT silencing results in cell cycle arrest, as well as the induction of autophagy and apoptosis, in bladder cancer cells (34,35). However, in rare cases, O-GlcNAcylation is decreased in cancer tissues such as ovarian cancer tissues which harbor high rates of p53 mutations (36).…”

Section: Imbalanced O-glcnacylation In Cancer Cellsmentioning

confidence: 63%

“…A similar phenomenon was revealed in bladder cancer cells and renal cell carcinoma (RCC). Knocking down OGT results in cell cycle arrest as well as induction of autophagy and apoptosis (34,35,117). Considering the critical function of aberrant O-GlcNAcylation in cancer progression and metastasis which has been summarized previously herein, it is likely that downregulation of hyper O-GlcNAcylation via OGT inhibition might not only slow cancer proliferation, but also cancer metastasis.…”

Section: Small Molecules That Target O-glcnacylationmentioning

confidence: 81%

Functional Analysis of O-GlcNAcylation in Cancer Metastasis

Jin

Qiu

et al. 2020

Front. Oncol.

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One common and reversible type of post-translational modification (PTM) is the addition of O-linked b-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), and its dynamic balance is controlled by O-GlcNAc transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA) through the addition or removal of O-GlcNAc groups. A large amount of research data confirms that proteins regulated by O-GlcNAcylation play a pivotal role in cells. In particularly, imbalanced levels of OGT and O-GlcNAcylation have been found in various types of cancers. Recently, increasing evidence shows that imbalanced O-GlcNAcylation directly or indirectly impacts the process of cancer metastasis. This review summarizes the current understanding of the influence of O-GlcNAc-proteins on the regulation of cancer metastasis. It will provide a theoretical basis to further elucidate of the molecular mechanisms underlying cancer emergence and progression.

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“…The GFAT inhibitor 6-diazo-5-oxo-norleucine (DON) can effectively reduce O-GlcNAcylation, and display cytotoxic effects in cell lines established from bladder cancer and acute myeloid leukemia. 19 , 20 However, in the Phase I and II clinical trials, this compound elicited adverse gastric-intestinal reactions, which limited its potentials for clinical application. 21 The N-acetylglucosamine-phosphate mutase (PGM3) inhibitor FR054 is a small molecule compound.…”

Section: Compounds Inhibiting O-glcnacylationmentioning

confidence: 99%