| Title |
COSMC knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer
|
|---|---|
| Published in |
Molecular Cancer, May 2015
|
| DOI | 10.1186/s12943-015-0386-1 |
| Pubmed ID | |
| Authors |
Bianca T. Hofmann, Laura Schlüter, Philip Lange, Baris Mercanoglu, Florian Ewald, Aljonna Fölster, Aeint-Steffen Picksak, Sönke Harder, Alexander T. El Gammal, Katharina Grupp, Cenap Güngör, Astrid Drenckhan, Hartmut Schlüter, Christoph Wagener, Jakob R. Izbicki, Manfred Jücker, Maximilian Bockhorn, Gerrit Wolters-Eisfeld |
| Abstract |
Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. Changes in O-glycosylation affect posttranslationally modified O-GalNAc proteins resulting in profound cellular alterations. Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. Expression of Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens was evaluated and correlated with clinicopathological data. Tn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. Nucleolin was identified as O-GalNAc modified protein in COSMC deficient PDAC cell lines. Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 33% |
| Practitioners (doctors, other healthcare professionals) | 1 | 33% |
| Scientists | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 104 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Argentina | 1 | <1% |
| Unknown | 103 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 15 | 14% |
| Student > Master | 13 | 13% |
| Student > Bachelor | 13 | 13% |
| Student > Ph. D. Student | 12 | 12% |
| Student > Postgraduate | 5 | 5% |
| Other | 16 | 15% |
| Unknown | 30 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 25 | 24% |
| Agricultural and Biological Sciences | 18 | 17% |
| Medicine and Dentistry | 12 | 12% |
| Immunology and Microbiology | 6 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 4% |
| Other | 8 | 8% |
| Unknown | 31 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 April 2021.
All research outputs
#6,391,095
of 23,577,654 outputs
Outputs from Molecular Cancer
#447
of 1,782 outputs
Outputs of similar age
#73,202
of 267,178 outputs
Outputs of similar age from Molecular Cancer
#12
of 45 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 1,782 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one has gotten more attention than average, scoring higher than 74% of its peers.
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We're also able to compare this research output to 45 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.