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Special Issue "O-GlcNAcylation and Cancer"

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 13706

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Special Issue Editors

Prof. Dr. Ikram El Yazidi-Belkoura

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Guest Editor

Université Lille, CNRS, UMR 8576—UGSF–Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France
Interests: O-GlcNAcylation; cell signaling; nutrition; colorectal cancer; 5-Fluorouracil response

Prof. Dr. Tony Lefebvre

E-Mail Website
Co-Guest Editor

Université Lille, CNRS, UMR 8576—UGSF–Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France
Interests: O-GlcNAcylation; cell signaling; cell cycle; colorectal and hepatic cancers; metabolism

Special Issue Information

Dear Colleagues,

Cancer is one of the leading causes of morbidity and mortality worldwide, linked in part to deteriorating environmental conditions and unsafe lifestyles. Much progress has been made in recent decades in deciphering the etiology, origin, and causes of cancer, but much remains to be done to understand the molecular mechanisms underlying its initiation and progression. In recent years, O-GlcNAcylation has been found to be particularly disturbed in oncogenic processes, irrespective of the stage or molecular process considered. In particular, because of its strategic position as a metabolic hub, this post-translational modification could play a role of switch between nutritional disorders and cancer. This Special Issue is an opportunity to take stock of current knowledge on the subject and to project research into the near future, which should shed new light into our understanding of the impact of a shaken O-GlcNAcylation homeostasis, related or not with the nutritional and environmental aspects, on cancer and anticancer therapies.

Prof. Dr. Ikram El Yazidi-Belkoura
Prof. Dr. Tony Lefebvre
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

cancer
O-GlcNAcylation
molecular mechanism
nutrition
metabolism
environment
therapy

Published Papers (6 papers)

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Research

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Open AccessArticle

Impact of Surgeon’s Experience in Rigid versus Elastic MRI/TRUS-Fusion Biopsy to Detect Significant Prostate Cancer Using Targeted and Systematic Cores

Magdalena Görtz

Joanne Nyaboe Nyarangi-Dix

Heinz-Peter Schlemmer

David Bonekamp

Markus Hohenfellner

and

Jan Philipp Radtke

Cancers 2022, 14(4), 886; https://doi.org/10.3390/cancers14040886 - 10 Feb 2022

Cited by 1 | Viewed by 1190

Abstract

Multiparametric magnetic resonance imaging (mpMRI) and MRI/ultrasound fusion-targeted prostate biopsy (FB) have excellent sensitivity in detecting significant prostate cancer (sPC). FB platforms can be distinguished by rigid (RTB) or elastic image registration (ETB). We compared RTB and ETB by analyzing sPC detection rates of both RTB and ETB at different stages of the surgeons’ learning curve. Patients undergoing RTB between 2015–2017 (n = 502) were compared to patients undergoing ETB from 2017–2019 (n = 437). SPC detection rates were compared by Chi-square-test on patient-basis. Combination of transperineal systematic biopsy and each TB served as reference and sub-analyses were performed for different grades of surgeon’s experience. In the RTB subgroup, 233 men (46%) had sPC, compared to 201 (46%) in the ETB subgroup. RTB alone detected 94% of men with sPC and ETB 87% (p = 0.02). However, for at least intermediate-experienced surgeons (>100 FB), no differences occurred between RTB and ETB. In the total cohort, at least intermediate-experienced surgeons detected significantly more sPC (10%, p = 0.008) than novices. Thus, targeted transperineal MRI/TRUS-FB with a RTB registration system showed a similar sPC detection rate to ETB in experienced surgeons but a superior sPC detection rate to ETB in the total cohort. Low-experienced surgeons seem to benefit from RTB. Full article

(This article belongs to the Special Issue O-GlcNAcylation and Cancer)

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Open AccessArticle

Comparative O-GlcNAc Proteomic Analysis Reveals a Role of O-GlcNAcylated SAM68 in Lung Cancer Aggressiveness

and

Cancers 2022, 14(1), 243; https://doi.org/10.3390/cancers14010243 - 04 Jan 2022

Cited by 3 | Viewed by 1882

Abstract

O-GlcNAcylation is a reversible and dynamic post-translational protein modification catalyzed by O-GlcNAc transferase (OGT). Despite the reported association of O-GlcNAcylation with cancer metastasis, the O-GlcNAc proteome profile for cancer aggressiveness remains largely uncharacterized. Here, we report our comparative O-GlcNAc proteome profiling of two differentially invasive lung adenocarcinoma cell lines, which identified 158 down-regulated and 106 up-regulated candidates in highly invasive cells. Among these differential proteins, a nuclear RNA-binding protein, SAM68 (SRC associated in mitosis of 68 kDa), was further investigated. Results showed that SAM68 is O-GlcNAcylated and may interact with OGT in the nucleus. Eleven O-GlcNAcylation sites were identified, and data from mutant analysis suggested that multiple serine residues in the N-terminal region are important for O-GlcNAcylation and the function of SAM68 in modulating cancer cell migration and invasion. Analysis of clinical specimens found that high SAM68 expression was associated with late cancer stages, and patients with high-OGT/high-SAM68 expression in their tumors had poorer overall survival compared to those with low-OGT/low-SAM68 expression. Our study revealed an invasiveness-associated O-GlcNAc proteome profile and connected O-GlcNAcylated SAM68 to lung cancer aggressiveness. Full article

(This article belongs to the Special Issue O-GlcNAcylation and Cancer)

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Open AccessArticle

Mitochondrial O-GlcNAc Transferase Interacts with and Modifies Many Proteins and Its Up-Regulation Affects Mitochondrial Function and Cellular Energy Homeostasis

Anne-Sophie Vercoutter-Edouart

Fabrice Bray

Tony Lefebvre

and

Anna Krześlak

Cancers 2021, 13(12), 2956; https://doi.org/10.3390/cancers13122956 - 12 Jun 2021

Cited by 12 | Viewed by 1979

Abstract

O-GlcNAcylation is a cell glucose sensor. The addition of O-GlcNAc moieties to target protein is catalyzed by the O-Linked N-acetylglucosamine transferase (OGT). OGT is encoded by a single gene that yields differentially spliced OGT isoforms. One of them is targeted to mitochondria (mOGT). Although the impact of O-GlcNAcylation on cancer cells biology is well documented, mOGT’s role remains poorly investigated. We performed studies using breast cancer cells with up-regulated mOGT or its catalytic inactive mutant to identify proteins specifically modified by mOGT. Proteomic approaches included isolation of mOGT protein partners and O-GlcNAcylated proteins from mitochondria-enriched fraction followed by their analysis by mass spectrometry. Moreover, we analyzed the impact of mOGT dysregulation on mitochondrial activity and cellular metabolism using a variety of biochemical assays. We found that mitochondrial OGT expression is glucose-dependent. Elevated mOGT expression affected the mitochondrial transmembrane potential and increased intramitochondrial ROS generation. Moreover, mOGT up-regulation caused a decrease in cellular ATP level. We identified many mitochondrial proteins as mOGT substrates. Most of these proteins are localized in the mitochondrial matrix and the inner mitochondrial membrane and participate in mitochondrial respiration, fatty acid metabolism, transport, translation, apoptosis, and mtDNA processes. Our findings suggest that mOGT interacts with and modifies many mitochondrial proteins, and its dysregulation affects cellular bioenergetics and mitochondria function. Full article

(This article belongs to the Special Issue O-GlcNAcylation and Cancer)

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Open AccessArticle

O-GlcNAcylation Links Nutrition to the Epigenetic Downregulation of UNC5A during Colon Carcinogenesis

Mathilde Body-Malapel

Eric Lelièvre

Olivier Coqueret

Dominique Leprince

Ikram El Yazidi-Belkoura

and

Vanessa Dehennaut

Cancers 2020, 12(11), 3168; https://doi.org/10.3390/cancers12113168 - 28 Oct 2020

Cited by 9 | Viewed by 2057

Abstract

While it is now accepted that nutrition can influence the epigenetic modifications occurring in colorectal cancer (CRC), the underlying mechanisms are not fully understood. Among the tumor suppressor genes frequently epigenetically downregulated in CRC, the four related genes of the UNC5 family: UNC5A, UNC5B, UNC5C and UNC5D encode dependence receptors that regulate the apoptosis/survival balance. Herein, in a mouse model of CRC, we found that the expression of UNC5A, UNC5B and UNC5C was diminished in tumors but only in mice subjected to a High Carbohydrate Diet (HCD) thus linking nutrition to their repression in CRC. O-GlcNAcylation is a nutritional sensor which has enhanced levels in CRC and regulates many cellular processes amongst epigenetics. We then investigated the putative involvement of O-GlcNAcylation in the epigenetic downregulation of the UNC5 family members. By a combination of pharmacological inhibition and RNA interference approaches coupled to RT-qPCR (Reverse Transcription-quantitative Polymerase Chain Reaction) analyses, promoter luciferase assay and CUT&RUN (Cleavage Under Target & Release Using Nuclease) experiments, we demonstrated that the O-GlcNAcylated form of the histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2) represses the transcription of UNC5A in human colon cancer cells. Collectively, our data support the hypothesis that O-GlcNAcylation could represent one link between nutrition and epigenetic downregulation of key tumor suppressor genes governing colon carcinogenesis including UNC5A. Full article

(This article belongs to the Special Issue O-GlcNAcylation and Cancer)

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Review

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Open AccessReview

Role and Function of O-GlcNAcylation in Cancer

Jii Bum Lee

Kyoung-Ho Pyo

and

Hye Ryun Kim

Cancers 2021, 13(21), 5365; https://doi.org/10.3390/cancers13215365 - 26 Oct 2021

Cited by 17 | Viewed by 2569

Abstract

Cancer cells are able to reprogram their glucose metabolism and retain energy via glycolysis even under aerobic conditions. They activate the hexosamine biosynthetic pathway (HBP), and the complex interplay of O-linked N-acetylglucosaminylation (O-GlcNAcylation) via deprivation of nutrients or increase in cellular stress results in the proliferation, progression, and metastasis of cancer cells. Notably, cancer is one of the emerging diseases associated with O-GlcNAcylation. In this review, we summarize studies that delineate the role of O-GlcNAcylation in cancer, including its modulation in metastasis, function with receptor tyrosine kinases, and resistance to chemotherapeutic agents, such as cisplatin. In addition, we discuss the function of O-GlcNAcylation in eliciting immune responses associated with immune surveillance in the tumor microenvironment. O-GlcNAcylation is increasingly accepted as one of the key players involved in the activation and differentiation of T cells and macrophages. Finally, we discuss the prognostic role of O-GlcNAcylation and potential therapeutic agents such as O-linked β-N-acetylglucosamine-transferase inhibitors, which may help overcome the resistance mechanism associated with the reprogramming of glucose metabolism. Full article

(This article belongs to the Special Issue O-GlcNAcylation and Cancer)

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Open AccessEditor’s ChoiceReview

O-GlcNAcylation and O-GlcNAc Cycling Regulate Gene Transcription: Emerging Roles in Cancer

Matthew P. Parker

Kenneth R. Peterson

and

Chad Slawson

Cancers 2021, 13(7), 1666; https://doi.org/10.3390/cancers13071666 - 01 Apr 2021

Cited by 30 | Viewed by 3221

Abstract

O-linked β-N-acetylglucosamine (O-GlcNAc) is a single sugar post-translational modification (PTM) of intracellular proteins linking nutrient flux through the Hexosamine Biosynthetic Pathway (HBP) to the control of cis-regulatory elements in the genome. Aberrant O-GlcNAcylation is associated with the development, progression, and alterations in gene expression in cancer. O-GlcNAc cycling is defined as the addition and subsequent removal of the modification by O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA) provides a novel method for cells to regulate various aspects of gene expression, including RNA polymerase function, epigenetic dynamics, and transcription factor activity. We will focus on the complex relationship between phosphorylation and O-GlcNAcylation in the regulation of the RNA Polymerase II (RNAP II) pre-initiation complex and the regulation of the carboxyl-terminal domain of RNAP II via the synchronous actions of OGT, OGA, and kinases. Additionally, we discuss how O-GlcNAcylation of TATA-box binding protein (TBP) alters cellular metabolism. Next, in a non-exhaustive manner, we will discuss the current literature on how O-GlcNAcylation drives gene transcription in cancer through changes in transcription factor or chromatin remodeling complex functions. We conclude with a discussion of the challenges associated with studying O-GlcNAcylation and present several new approaches for studying O-GlcNAc regulated transcription that will advance our understanding of the role of O-GlcNAc in cancer. Full article

(This article belongs to the Special Issue O-GlcNAcylation and Cancer)

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