Table 2 O-GlcNAc expression and roles in various cancers
Cancer type | Research object | O-GlcNAc | OGT | OGA | Major findings | Clinical | References |
|---|---|---|---|---|---|---|---|
Cervical cancer | HPV-related cervical tumors and human cervical cancer cell lines | Elevated | Elevated | no significant change | Elevated OGT activated the transcription of HPV E6/E7 and thus enhancing the oncogenic activity of HPV | Â | Zeng et al. (2016) |
| Â | The human cervical cancer cell lines | Elevated | Elevated | Na | Elevated OGT not only increased the expression of E6/E7 oncoproteins but also promoted HCF-1-mediated transcriptional activity of the E6/E7 promoter | Â | Xu et al. (2021) |
|  | The human cervical cell lines | Elevated | Elevated | Na | O-GlcNAcylation of NF-κB in cervical cancer promoted lung metastasis of cervical cancer by activating CXCR4 |  | Ali et al. (2017) |
Breast cancer | Primary breast malignant tumors | Elevated | Elevated | Na | Reduction of O-GlcNAcylation inhibited the anchorage-independent growth of breast cancer cells | Â | Champattanachai et al. (2013) |
|  | Breast cancer cell lines | Elevated | Elevated | Na | O-GlcNAcylation enhanced the migration/invasion of breast cancer cells in vitro and lung metastasis in vivo |  | Gu et al. (2010) |
| Â | Breast cancer cell lines | Elevated | Elevated | Na | Elevated O-GlcNAcylation and OGT levels contributed to cancer cell growth and invasion, | Â | Caldwell et al. (2010) |
| Â | Breast cancer cell lines | Elevated | Elevated | Na | Nutrient sensing pathway HBP connected with the SIRT1 deacetylase via O-GlcNAcylation to regulate cellular invasion via regulation of FOXM1 | Â | Ferrer et al. (2017) |
|  | Breast cancer stem cells | Elevated | Elevated | Na | OGT played a key role in the regulation of breast CSCs in vitro and tumor initiation in vivo |  | Akella et al. (2020) |
|  | HR + /HER2- luminal breast cancer patient samples | Elevated | Na | Na | Hyper-O-GlcNAcylation was associated with poor 10-year DFS in patients with breast cancer | Poor survival | Kuo et al. (2021) |
Endometrial cancer | Endometrial cancer patient samples | Na | Elevated | Elevated | The OGT and OGA expression were significantly higher in tumors of a higher histological grade and associated with the depth of tumor invasion into the myometrium | Â | Krzeslak et al. (2012) |
| Â | Endometrial cancer cell lines | Elevated | Na | Na | Hyper-O-GlcNAcylation promoted EMT in endometrial cancer cells | Â | Jaskiewicz and Townson (2019) |
OV | The human ovarian carcinoma cell lines | Elevated | Elevated | Na | O-GlcNAcylation decreased E-cadherin level, thereby inhibiting E-cadherin/catenin complex formation and reducing cell–cell adhesion, leading to cancer cell metastasis |  | Jin et al. (2013) |
| Â | The human ovarian carcinoma cell lines | Elevated | Elevated | Na | O-GlcNAcylation augments the motility of ovarian cancer cells via the RhoA/ROCK/MLC signaling pathway | Â | Niu et al. (2017) |
Liver cancer | HCC patient samples and cell lines | Elevated | Elevated | Na | O-GlcNAcylation of AGER increased its activity and stability to promote the development of HCC under high glucose conditions | Â | Qiao et al. (2016a) |
| Â | HCC patient samples and cell lines | Elevated | Elevated | Na | O-GlcNAcylation of HDAC1 was overexpressed in HCC, and the progression of HCC can be inhibited by inhibiting the O-GlcNAcylation of HDAC1 | Â | Zhu et al. (2016) |
| Â | Livers of diabetic mice | Elevated | Na | Na | There is positive auto-regulatory feedback between O-GlcNAcylation and TRIB2, which might be critical for diabetes-associated liver cancer | Â | Yao et al. (2016) |
| Â | HCC patient samples and cell lines | Elevated | Elevated | Na | ACSL4 promoted HCC growth and survival by enhancing O-GlcNAcylation and activating mTOR signaling. Conversely, O-GlcNAcylation facilitated HCC growth via increasing ACSL4 expression and activating mTOR signaling | Â | Wang et al. (2020) |
|  | NAFLD-HCC patient samples, and liver cancer cell lines | Na | Elevated | Na | OGT played an oncogenic role in NAFLD-associated HCC through regulating palmitic acid and inducing ER stress, consequently activating oncogenic JNK/c-Jun/AP-1 and NF-κB cascades |  | Xu et al. (2017) |
| Â | Samples from patients with HCC recurrence after liver transplantation | Elevated | Elevated | Decreased | O-GlcNAcylation was significantly enhanced in the tumor tissues of patients who had suffered from HCC recurrence after LT compared with those who had not. Importantly, low expression of OGA was an independent prognostic factor for predicting tumor recurrence of HCC following LT, especially in patients with low AFP expression | Poor Survival | Zhu et al. (2012) |
| Â | HCC patient samples | Elevated | Na | Na | Increased O-GlcNAcylation of RACK1 is positively correlated with tumor growth, metastasis, and recurrence in patients with HCC | Â | Duan et al. (2018) |
| Â | Liver cancer patient samples and cell lines | Elevated | Na | Na | YAP was O-GlcNAcylated at Thr241 thereby antagonizing Hippo pathway-mediated phosphorylation of YAP, thus allowing YAP to promote liver tumorigenesis under diabetes-prone, high-glucose conditions | Â | Zhang et al. (2017b) |
CRC | CRC patient samples and the human colon tumor cell lines | Elevated | Elevated | no significant change | O-GlcNAcylation enhanced the anchorage-independent growth of colon cancer cells | Â | Mi et al. (2011) |
| Â | CRC patient samples | Elevated | Elevated | no significant change | Abnormal O-GlcNAc-modified proteins, particularly annexin A2, may be novel biomarkers for CRC | Â | Phueaouan et al. (2013) |
| Â | CRC patient samples and the CRC cell lines | Elevated | Na | Na | O-GlcNAcylation at Thr236 of YY1 enhanced the expression of SLC22A15 and AANAT in cells and increase the protein stability of YY1 itself to exert its oncogenic effect | Â | Zhu et al. (2019) |
| Â | Human CRC cell lines | Elevated | Elevated | Na | Hyper-O-GlcNAcylation significantly contributed to tumor proliferation and metastasis and indicate a poor prognosis in patients with CRC | Poor survival | Wu et al. (2019) |
|  | The murine colon carcinoma cells | Elevated | Na | Na | O-GlcNAcylation deregulated β-catenin and E-cadherin expression and activity in fibroblast cell lines and this might influence EMT and cell motility, which may further influence tumor development and metastasis |  | Harosh-Davidovich and Khalaila (2018) |
| Â | Human colon cancer cells | Elevated | Elevated | Na | O-GlcNAcylation of XIAP at Ser406 is essential for its E3 ubiquitin ligase activity toward specifically OGT | Â | Seo et al. (2020) |
| Â | CRC patient samples, CRC cell lines | Elevated | Elevated | Na | ITGA5 overexpression accelerates the progression of CRC, which is closely associated with its enhanced O-GlcNAcylation | Â | Yu et al. (2019) |
PDAC | Human pancreatic cancer cells | Elevated | Elevated | Decreased | Hyper-O-GlcNAcylation played an important role in PDAC cells’ survival and constitutive NF-κB activity |  | Ma et al. (2013) |
|  | PDAC cells | Elevated | Elevated | Elevated | OGA promotes OGT transcription through cooperation with the histone acetyltransferase p300 and transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) |  | Qian et al. (2018) |
|  | The pancreatic cancer cell lines | Elevated | Elevated | Na | Triptolide-induced cell death in pancreatic cancer is mediated by alteration of O-GlcNAcylation of Sp1 |  | Banerjee et al. (2013) |
GC | Primary GC patient samples | Elevated | Elevated | Na | O-GlcNAcylation was associated with the carcinogenesis and progression of GC | Poor survival | Jang and Kim (2016) |
| Â | GC patient samples and cell lines | Elevated | Elevated | Na | Hyper-O-GlcNAcylation significantly promoted GC cell proliferation by modulating cell cycle-related proteins and ERK 1/2 signaling | Poor survival | Jiang et al. (2016) |
ESCC | ESCC patient samples | Elevated | Elevated | Na | Hyper-O-GlcNAcation stabilized proteins, leading to changes in cellular signal transduction and resulting in tumorigenesis and metastasis | Poor survival | Qiao et al. (2012) |
|  | ESCSs, ESCC cell lines | Na | Elevated | Na | OGT in exosomes from ECSCs protected ECSCs from CD8 + T cells through up-regulation of PD-1 |  | Yuan et al. (2021) |
CHOL | CHOL patient samples | Elevated | Elevated | Decreased | Hyper-O-GlcNAcylation in CHOL tissues was associated with poor patient outcomes | Poor Survival | Phoomak et al. (2012) |
PC | PC patient samples and cell lines | Elevated | Elevated | Na | OGT and O-GlcNAcylation were elevated in PC cells and required for growth, invasion, angiogenesis, and metastasis |  | Lynch et al. (2012) |
| Â | PC biopsy patient samples | Elevated | Na | Na | Hyper-O-GlcNAcylation was associated with decreased OS of patients | Poor Survival | Kamigaito et al. (2014) |
| Â | PC cell lines | Elevated | Elevated | Na | O-GlcNAcylation enhanced the malignancy of PC cells by inhibiting the formation of the E-cadherin/catenin/cytoskeleton complex | Â | Gu et al. (2014) |
| Â | PC patient samples | Na | Elevated | Na | Inhibition of OGT in PC cells resulted in slowing of the cell cycle and a reduction in DNA replication via a MYC-dependent pathway | Â | Itkonen et al. (2013) |
BC | Urine obtained from BC patients | Na | Elevated | Elevated | Analysis of urinary content of OGA and OGT mRNA was useful for bladder cancer diagnostics | Â | Rozanski et al. (2012) |
| Â | BC patient samples and cell lines | Elevated | Elevated | Na | Hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in BC | Â | Wang et al. (2018) |
| Â | BC patient samples and cell lines | Na | Elevated | Decreased | Knockdown of OGT inhibited cell proliferation, migration, invasion, and induce cell cycle arrest, while these effects were reversed when OGA is inhibited | Â | Jin et al. (2020a) |
RCC | RCC patient samples and cell lines | Elevated | Elevated | na | Hyper-O-GlcNAcylation was correlated with poor prognosis in RCC patients. OGT knockdown significantly suppressed RCC cell proliferation in vitro and in vivo | Poor survival | Wang et al. (2019) |
Lung cancer | Lung cancer patient samples and cell lines | Elevated | Elevated | na | Hyper-O-GlcNAcylation increased the growth and invasion of lung cancer cells | Â | Mi et al. (2011) |
| Â | LUAD patient samples | Elevated | Elevated | Elevated | High expression of OGT could independently predict poor survival outcomes in patients with stage I LUAD | Poor survival | Lin et al. (2018) |
|  | Lung cancer patient samples and LUAD cell lines | Elevated | Elevated | na | O-GlcNAcylation promoted migration and invasion by activating IL-6/STAT3 signaling in lung cancer |  | Ge et al. (2021a) |
SCLC | SCLC patient samples | Elevated | Elevated | Elevated | High OGT and OGA levels were associated with poor prognosis and could be considered new biomarkers of the invasive phenotype of tumor cells | Poor survival | Starska et al. (2015) |
CLL | Blood from CLL patients, CLL cells | Elevated | Elevated | Na | Indolent and aggressive clinical behavior of CLL cells were correlated with higher and lower O-GlcNAcylation levels, respectively | Â | Shi et al. (2010) |
AML | AML patient samples and cell lines | Na | Elevated | Na | Elevated OGT expression was significantly associated with poor OS in patients with AML. Inhibition of OGT inhibited AML cell proliferation and promoted AML cell apoptosis | Poor survival | He et al. (2021) |
| Â | AML patient samples and cell lines | Elevated | Elevated | Na | Inhibition of HBP or OGT led to AML cell differentiation and apoptosis | Â | Asthana et al. (2018) |
ALL | Pre-B ALL patient samples and cell lines | Elevated | Elevated | Decreased | O-GlcNAcylation aggravated pre-B-ALL through regulation of glycolysis via the PI3K/Akt/c-Myc pathway | Â | Zhang et al. (2017a) |
DLBC | DLBC patient samples and cell lines | Elevated | Elevated | Na | Elevated OGT levels were associated with poor survival of patients with DLBC. Targeting OGT in DLBC cells inhibited activation of O-GlcNAcylation and NF-κB | Poor survival | Pham et al. (2016) |
TC | TC patient samples | Decreased | na | Elevated | OGA activity increased in TC in comparison to non-neoplastic lesions and adenomas | Â | Krzeslak et al. (2010) |
| Â | Papillary thyroid cancer patient samples and cell lines | Elevated | Elevated | Na | O-GlcNAcylation of YAP at Ser109 dramatically inhibited its Ser127 phosphorylation, subsequently promoting tumor aggressiveness | Poor survival | Li et al. (2021a) |
GBM | GBM patient samples | Elevated | Elevated | Na | OGT regulates acetate-dependent acetyl-CoA and lipid production in GBM cells by regulating phosphorylation of ACSS2 by CDK5 | Â | Ciraku et al. (2022) |