ppGalNAc T1 as a Potential Novel Marker for Human Bladder Cancer

Ding, Mei; Wang, Haifeng; Wang, Jiansong; Zhan, Hui; Zuo, Yigang; Yang, Delin; Liu, Jingyu; Wang, Wei; Ke, Changxing; Yan, Ran

doi:10.7314/apjcp.2012.13.11.5653

Cited by 20 publications

(13 citation statements)

References 13 publications

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“…Thus, GALNT6 and GALNT13 display elevated levels in different cancer types, including breast and gastric carcinomas (GALNT6) and lung cancer and neuroblastoma (GALNT13) , as both genes are found to be associated with tumor invasion and metastasis [44–47]. Similarly, GALNT14 knockdown significantly suppresses the cell migration and altered cellular morphology of EOC cells [48], and GALNT1 knockdown inhibits proliferation and tumor growth of bladder cancer cells [49], while GALNT10 expression positively correlates with histological type and degree of differentiation of gastric cancer [50]. In contrast, GALNT2 exerts anti-proliferative and anti-metastatic activity in gastric, brain and hepatocellular carcinomas [51–53], while GALNT9 is positively associated with a better clinical outcome in neuroblastoma patients [54], and GALNT12 expression represents a negative marker especially of metastatic gastric and colorectal cancer [55].…”

Section: Discussionmentioning

confidence: 99%

Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation

et al. 2014

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Previously, we have identified the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) gene as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that GALNT3 is strongly overexpressed in HG serous EOC tumors as compared to normal ovarian tissue. Moreover, the GALNT3 expression significantly correlated with shorter progression-free survival (PFS) intervals in epithelial ovarian cancer (EOC) patients with advanced disease.Knockdown of the GALNT3 expression in EOC cells led to sharp decrease of cell proliferation and induced S-phase cell cycle arrest. Additionally, GALNT3 suppression significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon GALNT3 suppression, while some tumor suppressor genes were induced. Moreover, GALNT3 downregulation was associated with reduced MUC1 protein expression in EOC cells, probably related to destabilization of the MUC1 protein due to lack of GALNT3 glycosylation activity. GALNT3 knockdown was also accompanied with increase of the cell adhesion molecules β-catenin and E-cadherin, which are normally suppressed by MUC1 in cancer, thus supporting the role of the GALNT3-MUC1 axis in EOC invasion.Taken together, our data are indicative for a strong oncogenic potential of the GALNT3 gene in advanced EOC and identify this transferase as a novel EOC biomarker and putative EOC therapeutic target. Our findings also suggest that GALNT3 overexpression might contribute to EOC progression through aberrant mucin O-glycosylation

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Section: Discussionmentioning

confidence: 99%

Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation

et al. 2014

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“…Both genes have been reported to be involved in bladder cancer progression [39,40]. GALNT1 has an important role in transforming growth factor signaling [41], and it has been suggested as a possible biomarker of bladder cancer [42]. A similar situation occurs with LASS2 .…”

Section: Discussionmentioning

confidence: 99%

A Pilot Study on the Potential of RNA-Associated to Urinary Vesicles as a Suitable Non-Invasive Source for Diagnostic Purposes in Bladder Cancer

Pérez

Loizaga

Arceo

et al. 2014

Cancers

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Bladder cancer is one of the most common cancers and, together with prostate carcinoma, accounts for the majority of the malignancies of the genitourinary tract. Since prognosis ameliorates with early detection, it will be beneficial to have a repertoire of diagnostic markers that could complement the current diagnosis protocols. Recently, cell-secreted extracellular vesicles have received great interest as a source of low invasive disease biomarkers because they are found in many body fluids, including urine. The current work describes a pilot study to generate an array-based catalogue of mRNA associated to urinary vesicles, and also a comparison with samples obtained from bladder cancer patients. After an analysis of presence/absence of transcripts in bladder cancer EVs, a list of genes was selected for further validation using PCR technique. We found four genes differentially expressed in cancer samples. LASS2 and GALNT1 were present in cancer patients, while ARHGEF39 and FOXO3 were found only in non-cancer urinary vesicles. Previous studies have pointed to the involvement of those genes in tumour progression and metastasis.

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“…These enzymes possess housekeeping functions and are ubiquitously expressed at a low level. Silencing the expression of ppGalNAc-T1 inhibited the proliferation and tumor growth of bladder cancer (39). A previous study indicated that ppGalNAc-T2 regulates cellular metastatic behavior in gastric cancer (40).…”

Section: Discussionmentioning

confidence: 93%

RNA interference-mediated silencing of ppGalNAc-T1 and ppGalNAc-T2 inhibits invasion and increases chemosensitivity potentially by reducing terminal α2,3 sialylation and MMP14 expression in triple-negative breast cancer cells

Qiu

Liu

et al. 2017

Molecular Medicine Reports

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Glycopeptide-preferring polypeptide N-acetylgalactosamine transferase (ppGalNAc‑T) is a key enzyme that initiates the formation of the first GalNAc monosaccharide to polypeptides at Thr/Ser residues by O‑linked glycosylation. In order to investigate the effects of ppGalNAc‑T1 and ppGalNAc‑T2 on the initiation of O‑glycosylation, siRNA‑ppGalNAc‑T1 (si‑T1) and siRNA‑ppGalNAc‑T2 (si‑T2) were transfected into highly‑invasive estrogen receptor‑negative MDA‑MB‑231 cells to inhibit O‑glycosylation. Downregulation of ppGalNAc‑T1 demonstrated a significant reduction in the number of terminal α2,3 sialic acids, when compared to cells transfected with si‑T2 or si‑T1/T2. This downregulation led to a decrease in the invasion capabilities of the breast carcinoma cells, as well as enhanced chemosensitivity, which was the result antineoplastic drug effects. In addition, immunoprecipitation assays demonstrated that downregulation of ppGalNAc‑T1 led to a reduction in the number of terminal α2,3 sialic acids on O‑linked glycans of the matrix metalloproteinase‑14 (MMP14) glycoprotein. Furthermore, MMP14 and vascular endothelial growth factor were downregulated in the si‑T1 groups when compared with the si‑T2 and si‑T1/T2 groups. In conclusion, the results of the present study suggest that ppGalNAc‑T1 may serve a pivotal role in the initiation of O‑glycosylation, which may lead to a low density of α2,3 sialic acids on O‑linked glycans of MMP14 when downregulated. Glycosylation serves a significant role in regulating the sensitivity of MMP14 to self‑proteolysis, which ultimately decreases the invasion capabilities of breast cancer cells. The results of the present study may be useful in establishing the function of ppGalNAc‑T1 during breast cancer invasion and metastasis.

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ppGalNAc T1 as a Potential Novel Marker for Human Bladder Cancer

Cited by 20 publications

References 13 publications

Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation

Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation

A Pilot Study on the Potential of RNA-Associated to Urinary Vesicles as a Suitable Non-Invasive Source for Diagnostic Purposes in Bladder Cancer

RNA interference-mediated silencing of ppGalNAc-T1 and ppGalNAc-T2 inhibits invasion and increases chemosensitivity potentially by reducing terminal α2,3 sialylation and MMP14 expression in triple-negative breast cancer cells

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