Evidence map›Paper›PMID 32203219›Full record

ArticleBritish journal of cancer2020

Global analysis of human glycosyltransferases reveals novel targets for pancreatic cancer pathogenesis.

Rohitesh Gupta, Frank Leon, Christopher M Thompson, Ramakrishna Nimmakayala, Saswati Karmakar, Palanisamy Nallasamy, Seema Chugh, Dipakkumar R Prajapati, Satyanarayana Rachagani, Sushil Kumar and 1 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 62 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Rohitesh GuptaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Frank LeonDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Christopher M ThompsonDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Ramakrishna NimmakayalaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Saswati KarmakarDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Palanisamy NallasamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Seema ChughDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Dipakkumar R PrajapatiDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
Satyanarayana RachaganiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Sushil KumarDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Moorthy P PonnusamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. mpalanim@unmc.edu.
University of Nebraska Medical Center · US

Funding

Project 3: MUC16-Mediated Metabolic Reprograming Induces PC MetastasisP01CA217798 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI HOLLINGSWORTH, MICHAEL A. · 2018 to 2022
$8.1M
Role of PD2/Paf1 in Pancreatic Acinar to Ductal MetaplasiaR01CA210637 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., PONNUSAMY, MOORTHY P. · 2017 to 2021
$2.0M
Mucin Splice Variants in Pancreatic Cancer Diagnosis and PathogenesisF31CA243469 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI THOMPSON, CHRISTOPHER MICHAEL · 2019 to 2020
$84k
NCI NIH HHS F31 CA243469NCI NIH HHS P01 CA217798NCI NIH HHS R01 CA210637
6 · The paper itself

Abstract

backgroundSeveral reports have shown the role of glycosylation in pancreatic cancer (PC), but a global systematic screening of specific glycosyltransferases (glycoTs) in its progression remains unknown.

methodsWe demonstrate a rigorous top-down approach using TCGA-based RNA-Seq analysis, multi-step validation using RT-qPCR, immunoblots and immunohistochemistry. We identified six unique glycoTs (B3GNT3, B4GALNT3, FUT3, FUT6, GCNT3 and MGAT3) in PC pathogenesis and studied their function using CRISPR/Cas9-based KD systems.

resultsSerial metastatic in vitro models using T3M4 and HPAF/CD18, generated in house, exhibited decreases in B3GNT3, FUT3 and GCNT3 expression on increasing metastatic potential. Immunohistochemistry identified clinical significance for GCNT3, B4GALNT3 and MGAT3 in PC. Furthermore, the effects of B3GNT3, FUT3, GCNT3 and MGAT3 were shown on proliferation, migration, EMT and stem cell markers in CD18 cell line. Talniflumate, GCNT3 inhibitor, reduced colony formation and migration in T3M4 and CD18 cells. Moreover, we found that loss of GCNT3 suppresses PC progression and metastasis by downregulating cell cycle genes and β-catenin/MUC4 axis. For GCNT3, proteomics revealed downregulation of MUC5AC, MUC1, MUC5B including many other proteins.

conclusionsCollectively, we demonstrate a critical role of O- and N-linked glycoTs in PC progression and delineate the mechanism encompassing the role of GCNT3 in PC.

Indexed as

AnimalsGene Expression Regulation, NeoplasticGlycosyltransferasesHumansN-AcetylglucosaminyltransferasesPancreatic NeoplasmsSequence Analysis, RNAbeta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3GlycosyltransferasesN-Acetylglucosaminyltransferases

Identifiers

PMID32203219
PMCPMC7251111
OpenAlexW3011000971

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.