Dataset Information

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

ABSTRACT:

Background

Several 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.

Methods

We 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.

Results

Serial 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.

Conclusions

Collectively, 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.

SUBMITTER: Gupta R

PROVIDER: S-EPMC7251111 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

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

Gupta Rohitesh R Leon Frank F Thompson Christopher M CM Nimmakayala Ramakrishna R Karmakar Saswati S Nallasamy Palanisamy P Chugh Seema S Prajapati Dipakkumar R DR Rachagani Satyanarayana S Kumar Sushil S Ponnusamy Moorthy P MP

British journal of cancer 20200319 11

<h4>Background</h4>Several 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.<h4>Methods</h4>We 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 f ...[more]

PMID: 32203219

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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