Sweet and Sour: The Impact of Differential Glycosylation in Cancer Cells Undergoing Epithelial–Mesenchymal Transition

Glycosylation changes are a feature of disease states. One clear example is cancer cells, which commonly express glycans at atypical levels or with different structural attributes than those found in normal cells. Epithelial–mesenchymal transition (EMT) was initially recognized as an important step for morphogenesis during embryonic development, and is now shown to be one of the key steps promoting tumor metastasis. Cancer cells undergoing EMT are characterized by significant changes in glycosylation of the extracellular matrix (ECM) components and cell-surface glycoconjugates. Current scientific methodology enables all hallmarks of EMT to be monitored in vitro and this experimental model has been extensively used in oncology research during the last 10 years. Several studies have shown that cell-surface carbohydrates attached to proteins through the amino acids, serine, or threonine (O-glycans), are involved in tumor progression and metastasis, however, the impact of O-glycans on EMT is poorly understood. Recent studies have demonstrated that transforming growth factor-beta (TGF-β), a known EMT inducer, has the ability to promote the up-regulation of a site-specific O-glycosylation in the IIICS domain of human oncofetal fibronectin, a major ECM component expressed by cancer cells and embryonic tissues. Armed with the knowledge that cell-surface glycoconjugates play a major role in the maintenance of cell homeostasis and that EMT is closely associated with glycosylation changes, we may benefit from understanding how unusual glycans can govern the molecular pathways associated with cancer progression. This review initially focuses on some well-known changes found in O-glycans expressed by cancer cells, and then discusses how these alterations may modulate the EMT process.

• Publication year

  2014

• Venue

  Frontiers in Oncology

• Publication date

  2014-03-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fonc.2014.00059PMID 24724053PMCID 3971198
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• MUC1 drives epithelial-mesenchymal transition in renal carcinoma through Wnt/β-catenin pathway and interaction with SNAIL promoter.

  2014cited by this paper
• Tissue kallikrein mediates neurite outgrowth through epidermal growth factor receptor and flotillin-2 pathway in vitro.

  2014cited by this paper
• Angiogenesis stimulated by human kallikrein‐related peptidase 12 acting via a platelet‐derived growth factor B‐dependent paracrine pathway

  2014cited by this paper
• Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation

  2014cited by this paper
• β-catenin is O-GlcNAc glycosylated at Serine 23: implications for β-catenin's subcellular localization and transactivator function.

  2014cited by this paper
• MUC1-C oncoprotein activates the ZEB1/miR-200c regulatory loop and epithelial–mesenchymal transition

  2014cited by this paper
• Coagulation and metastasis: what does the experimental literature tell us?

  2013cited by this paper
• Increase of O-Glycosylated Oncofetal Fibronectin in High Glucose-Induced Epithelial-Mesenchymal Transition of Cultured Human Epithelial Cells

  2013cited by this paper
• Differential expression profiles of glycosphingolipids in human breast cancer stem cells vs. cancer non-stem cells

  2013cited by this paper
• Preoperative carcinoembryonic antigen as an outcome predictor in colon cancer

  2013cited by this paper
• Obesity, diabetes, and survival outcomes in a large cohort of early-stage breast cancer patients.

  2013cited by this paper
• Epithelial–mesenchymal plasticity in carcinoma metastasis

  2013cited by this paper
• Comparative genomics as a tool to understand evolution and disease

  2013influential reference
• Tn and sialyl‐Tn antigens, aberrant O‐glycomics as human disease markers

  2013cited by this paper
• CD43 in the nucleus and cytoplasm of lung cancer is a potential therapeutic target

  2013cited by this paper
• Monoclonal antibodies toward different Tn-amino acid backbones display distinct recognition patterns on human cancer cells. Implications for effective immuno-targeting of cancer

  2013cited by this paper
• Protein O-mannosylation is crucial for E-cadherin–mediated cell adhesion

  2013influential reference
• Dual Coordination of Post Translational Modifications in Human Protein Networks

  2013cited by this paper
• Altered glycosylation of MUC1 influences its association with CIN85: the role of this novel complex in cancer cell invasion and migration

  2013cited by this paper
• A correlation between altered O-GlcNAcylation, migration and with changes in E-cadherin levels in ovarian cancer cells.

  2013cited by this paper
• Emerging role of mucins in epithelial to mesenchymal transition.

  2013cited by this paper
• Post-translational modification: A SUMO protease for stress protection

  2013cited by this paper
• Diabetes mellitus and cancer risk: Review of the epidemiological evidence

  2013cited by this paper
• Tumor and its microenvironment: a synergistic interplay.

  2013cited by this paper
• Anti-Diabetic Medications and Risk of Pancreatic Cancer in Patients With Diabetes Mellitus: A Systematic Review and Meta-Analysis

  2013cited by this paper
• Role of Epithelial-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma: Is Tumor Budding the Missing Link?

  2013cited by this paper
• Exploring the Glycosylation of Serum CA125

  2013cited by this paper
• Mortality After Incident Cancer in People With and Without Type 2 Diabetes

  2012cited by this paper
• Diabetes and cancer II: role of diabetes medications and influence of shared risk factors

  2012cited by this paper
• Sialic acid: a sweet swing between mammalian host and Trypanosoma cruzi

  2012cited by this paper
• Induction of epithelial‐mesenchymal transition with O‐glycosylated oncofetal fibronectin

  2012influential reference
• Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

  2012cited by this paper
• Cancer Cell Adhesion and Metastasis: Selectins, Integrins, and the Inhibitory Potential of Heparins

  2012cited by this paper
• Loss and Recovery of Mgat3 and GnT-III Mediated E-cadherin N-glycosylation Is a Mechanism Involved in Epithelial-Mesenchymal-Epithelial Transitions

  2012cited by this paper
• MortalityAfter Incident Cancer in People With andWithout Type 2 Diabetes Impact of metformin on survival

  2012cited by this paper
• Roles of N-Acetylglucosaminyltransferase III in Epithelial-to-Mesenchymal Transition Induced by Transforming Growth Factor β1 (TGF-β1) in Epithelial Cell Lines*

  2012cited by this paper
• Two opposing roles of O-glycans in tumor metastasis.

  2012influential reference
• Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation

  2012cited by this paper
• Carbohydrate to carbohydrate interaction in development process and cancer progression

  2012cited by this paper
• Branched N-glycans and their implications for cell adhesion, signaling and clinical applications for cancer biomarkers and in therapeutics.

  2011cited by this paper
• The physics of cancer: the role of physical interactions and mechanical forces in metastasis

  2011cited by this paper
• Location, location, location: new insights into O-GalNAc protein glycosylation.

  2011cited by this paper
• Aberrant glycosylation associated with enzymes as cancer biomarkers

  2011cited by this paper
• Fibronectin splice variants: Understanding their multiple roles in health and disease using engineered mouse models

  2011cited by this paper
• Involvement of O-glycosylation defining oncofetal fibronectin in epithelial-mesenchymal transition process

  2011cited by this paper
• Diabetes mellitus and breast cancer outcomes: a systematic review and meta-analysis.

  2011cited by this paper
• Blocking core fucosylation of TGF-β1 receptors downregulates their functions and attenuates the epithelial-mesenchymal transition of renal tubular cells.

  2011cited by this paper
• Alpha fetoprotein is more than a hepatocellular cancer biomarker: from spontaneous immune response in cancer patients to the development of an AFP-based cancer vaccine.

  2011cited by this paper
• Small Changes Huge Impact: The Role of Protein Posttranslational Modifications in Cellular Homeostasis and Disease

  2011influential reference
• Trypanosoma cruzi Subverts Host Cell Sialylation and May Compromise Antigen-specific CD8+ T Cell Responses*

  2010cited by this paper
• A Systematic Review and Meta-analysis

  2010cited by this paper
• Glycogene Expression Alterations Associated with Pancreatic Cancer Epithelial-Mesenchymal Transition in Complementary Model Systems

  2010cited by this paper
• Increased immunogenicity of tumor-associated antigen, mucin 1, engineered to express alpha-gal epitopes: a novel approach to immunotherapy in pancreatic cancer.

  2010influential reference
• Fibronectin synthesis by high glucose level mediated proliferation of mouse embryonic stem cells: Involvement of ANG II and TGF‐β1

  2010cited by this paper
• Functional role of gangliotetraosylceramide in epithelial-to-mesenchymal transition process induced by hypoxia and by TGF-{beta}.

  2010cited by this paper
• Snail1 is stabilized by O‐GlcNAc modification in hyperglycaemic condition

  2010cited by this paper
• Tumors as organs: complex tissues that interface with the entire organism.

  2010cited by this paper
• MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition

  2010cited by this paper
• Diabetes and Cancer

  2010cited by this paper
• Sweetening the pot: adding glycosylation to the biomarker discovery equation.

  2010cited by this paper
• Biomarkers for epithelial-mesenchymal transitions.

  2009cited by this paper
• Cancer cells in transit: the vascular interactions of tumor cells.

  2009cited by this paper
• Differential N-glycosylation of Kallikrein 6 Derived from Ovarian Cancer Cells or the Central Nervous System*

  2009cited by this paper
• Compensation of loss of protein function in microsatellite-unstable colon cancer cells (HCT116): a gene-dependent effect on the cell surface glycan profile.

  2009cited by this paper
• Control of cell motility by interaction of gangliosides, tetraspanins, and epidermal growth factor receptor in A431 versus KB epidermoid tumor cells.

  2009cited by this paper
• Altered Glycosylation in Tumours Focused to Cancer Diagnosis

  2009cited by this paper
• Specific glycosphingolipids mediate epithelial-to-mesenchymal transition of human and mouse epithelial cell lines

  2009cited by this paper
• Epithelial-mesenchymal transitions in development and disease.

  2009cited by this paper
• Matrix crosslinking forces tumor progression by enhancing integrin signaling.

  2009cited by this paper
• Recent insights into the biological roles of mucin-type O-glycosylation

  2009cited by this paper
• Epithelial-mesenchymal transition: a cancer researcher's conceptual friend and foe.

  2009cited by this paper
• The basics of epithelial-mesenchymal transition.

  2009cited by this paper
• N-Glycans in cancer progression.

  2008cited by this paper
• Three-dimensional context regulation of metastasis

  2008cited by this paper
• Mucin-type O-glycosylation and its potential use in drug and vaccine development.

  2008cited by this paper
• IIICS de novo glycosylated fibronectin as a marker for invasiveness in urothelial carcinoma of the urinary bladder (UBC)

  2008cited by this paper
• O-GlcNAc-glycosylation of beta-catenin regulates its nuclear localization and transcriptional activity.

  2008cited by this paper
• Mucin glycosylation is altered by pro-inflammatory signaling in pancreatic-cancer cells.

  2008cited by this paper
• Mammalian glycosylation in immunity

  2008cited by this paper
• Is Sialyl Lewis x Antigen Expression a Prognostic Factor in Patients With Breast Cancer?

  2008cited by this paper
• Distribution of 15 human kallikreins in tissues and biological fluids.

  2007cited by this paper
• Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence.

  2007cited by this paper
• Biological significance of cancer-associated sialyl-Tn antigen: modulation of malignant phenotype in gastric carcinoma cells.

  2007cited by this paper
• Galectin-3 Interaction with Thomsen-Friedenreich Disaccharide on Cancer-associated MUC1 Causes Increased Cancer Cell Endothelial Adhesion*

  2007cited by this paper
• Stabilization of Plakoglobin and Enhanced Keratinocyte Cell-Cell Adhesion by Intracellular O-Glycosylation*

  2006cited by this paper
• Glycosylation in cellular mechanisms of health and disease.

  2006cited by this paper
• Asparagine-linked protein glycosylation: from eukaryotic to prokaryotic systems.

  2006cited by this paper
• Glycans in cancer and inflammation — potential for therapeutics and diagnostics

  2005cited by this paper
• Tensional homeostasis and the malignant phenotype.

  2005cited by this paper
• Self-Renewal and Cancer of the Gut: Two Sides of a Coin

  2005influential reference
• Protein glycosylation in bacterial mucosal pathogens

  2005cited by this paper
• Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment?

  2005cited by this paper
• Two Sides of a Coin

  2004cited by this paper
• Hyperglycemia‐induced TGFβ and fibronectin expression in embryonic mouse heart

  2004cited by this paper
• The emerging roles of human tissue kallikreins in cancer

  2004cited by this paper
• Post-translational modifications and their biological functions: proteomic analysis and systematic approaches.

  2004influential reference
• Glycans and neural cell interactions

  2004cited by this paper
• Friends or foes — bipolar effects of the tumour stroma in cancer

  2004cited by this paper
• Tumor cell surface carbohydrate and the metastatic phenotype

  2004cited by this paper
• Stromal fibroblasts in cancer initiation and progression

  2004cited by this paper

• Control of regulatory T cell differentiation and function by glycan remodeling.

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• Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate

  2024cites this paper
• Non-self glycan structures as possible modulators of cancer progression: would polysaccharides from Cryptococcus spp. impact this phenomenon?

  2023cites this paper
• Bittersweet Sugars: How Unusual Glycan Structures May Connect Epithelial-to-Mesenchymal Transition and Multidrug Resistance in Cancer

  2023cites this paper
• Increased Expression of the Pathological O-glycosylated Form of Oncofetal Fibronectin in the Multidrug Resistance Phenotype of Cancer Cells.

  2023cites this paper
• The Blessed Union of Glycobiology and Immunology: A Marriage That Worked

  2023cites this paper
• Glycosylated proteins with abnormal glycosylation changes are potential biomarkers for early diagnosis of breast cancer.

  2023cites this paper
• An odorant-binding protein in the elephant's trunk is finely tuned to sex pheromone (Z)-7-dodecenyl acetate

  2022cites this paper
• A systematic review of prognosis of ABO blood group and rhesus factor on outcomes in patients with bladder cancer

  2022cites this paper
• Glycobiology of Cancer: Sugar Drives the Show

  2022cites this paper
• Expression of O-glycosylated oncofetal fibronectin in alternatively activated human macrophages

  2022cites this paper
• Construction of mouse cochlin mutants with different GAG-binding specificities and their use for immunohistochemistry

  2022cites this paper
• Modifying effects of nerolidol on cell surface glycoconjugates and suppressed inflammation during DMBA-induced oral carcinogenesis: An in vivo and in silico

  2022cites this paper
• Glycobiology of the Epithelial to Mesenchymal Transition

  2021cites this paper
• Tissue-specific control of galectin-1-driven circuits during inflammatory responses.

  2021cites this paper
• High B3GALT5 expression confers poor clinical outcome and contributes to tumor progression and metastasis in breast cancer

  2021cites this paper
• Glycosylation of Stem Cells

  2021cites this paper
• Cardiac glycosaminoglycans and structural alterations during chronic stress-induced depression-like behavior in mice.

  2021cites this paper
• Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells

  2020cites this paper
• 3D Extracellular matrix mimics: fundamental concepts and role of materials chemistry to influence the stem cell fate.

  2020cites this paper
• Glycosylation on Unprotected or Partially Protected Acceptors

  2020cites this paper
• Aberrant sialylation in ovarian cancers.

  2020cites this paper
• ppGalNAc-T4-catalyzed O-Glycosylation of TGF-β type Ⅱ receptor regulates breast cancer cells metastasis potential.

  2020cites this paper
• Heparan Sulfate Proteoglycans Can Promote Opposite Effects on Adhesion and Directional Migration of Different Cancer Cells.

  2020cites this paper
• ppGalNAc-T4-catalyzed O-Glycosylation of TGF-β type Ⅱ receptor regulates breast cancer cells metastasis potential

  2020cites this paper
• Resistance to paclitaxel induces glycophenotype changes and mesenchymal-to-epithelial transition activation in the human prostate cancer cell line PC-3

  2020cites this paper
• Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer

  2020cites this paper
• Probing the recognition specificity of αVβ1 integrin and syndecan-4 using force spectroscopy.

  2020cites this paper
• N-Glycoproteomic Profiling Reveals Alteration In Extracellular Matrix Organization In Non-Type Bladder Carcinoma

  2019cites this paper
• Glycans in nanomedicine, impact and perspectives.

  2019cites this paper
• Hexosamine Biosynthetic Pathway and Glycosylation Regulate Cell Migration in Melanoma Cells

  2019cites this paper
• Don’t sugarcoat it: How glycocalyx composition influences cancer progression

  2019cites this paper
• Glycosylation of Cancer Stem Cells: Function in Stemness, Tumorigenesis, and Metastasis

  2018cites this paper
• Extracellular vesicle-mediated EBAG9 transfer from cancer cells to tumor microenvironment promotes immune escape and tumor progression

  2018cites this paper
• Metabolic Symbiosis and Immunomodulation: How Tumor Cell-Derived Lactate May Disturb Innate and Adaptive Immune Responses

  2018cites this paper
• Surfactant and Chaotropic Agent Assisted Sequential Extraction/On-Pellet Digestion (SCAD) for Enhanced Proteomics.

  2018cites this paper
• Serum N-glycome alterations in colorectal cancer associate with survival

  2018cites this paper
• From an increase in the number of tandem repeats through the decrease of sialylation to the downregulation of MUC1 expression level

  2018cites this paper
• Identification and characterization of glycobiomarkers in bladder cancer stem cells

  2018cites this paper
• GnT 8 regulates oxaliplatin resistance by altering integrin β 1 glycosylation in colon cancer cells

  2018cites this paper
• 3-Bromopyruvate treatment induces alterations of metabolic and stress-related pathways in glioblastoma cells.

  2017cites this paper
• Harnessing cancer cell metabolism for theranostic applications using metabolic glycoengineering of sialic acid in breast cancer as a pioneering example.

  2017cites this paper
• High mannose N-glycan binding lectin from Remusatia vivipara (RVL) limits cell growth, motility and invasiveness of human breast cancer cells.

  2017cites this paper
• Insights into the role of sulfated glycans in cancer cell adhesion and migration through use of branched peptide probe

  2016cites this paper
• Sugars and cell adhesion: the role of ST6GalNAc1 in prostate cancer progression

  2016cites this paper
• Glycosylated Notch and Cancer

  2016cites this paper
• Aberrant sialylation of a prostate-specific antigen: Electrochemical label-free glycoprofiling in prostate cancer serum samples.

  2016cites this paper
• Mechanisms of cisplatin resistance and targeting of cancer stem cells: Adding glycosylation to the equation.

  2016cites this paper
• Mechanisms of disease: The human N-glycome.

  2016cites this paper
• Role of Glycans in Cancer Cells Undergoing Epithelial–Mesenchymal Transition

  2016cites this paper
• Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines

  2016cites this paper
• Protein glycosylation in cancers and its potential therapeutic applications in neuroblastoma

  2016cites this paper
• Targeting Selectins and Their Ligands in Cancer

  2016cites this paper
• Newcastle Disease Virus Hemagglutinin Neuraminidase as a Potential Cancer Targeting Agent

  2016cites this paper
• The Sweet Side of Immune Evasion: Role of Glycans in the Mechanisms of Cancer Progression

  2016cites this paper
• Glycosylation in Cancer: Interplay between Multidrug Resistance and Epithelial-to-Mesenchymal Transition?

  2016cites this paper
• Glycosylation and cancer: moving glycomics to the forefront.

  2015cites this paper
• Article Open Access

  2015cites this paper
• The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer

  2015cites this paper
• miRNA proxy approach reveals hidden functions of glycosylation

  2015cites this paper
• The impact of the AB0 and the Rhesus blood group system on outcomes in bladder cancer patients treated with radical cystectomy

  2015cites this paper
• Sugar tags and tumorigenesis

  2015cites this paper
• Engineering yeast for producing human glycoproteins: where are we now?

  2015cites this paper
• Novel O-glycan arrays to characterize human cancer-associated epithelial antigens

  2015cites this paper
• Der Einfluss des Osteoblasten- und Tumorzellfibronektins auf die Immunzellen

  2015cites this paper
• Recent advances and challenges in plant phosphoproteomics

  2015cites this paper
• New approaches for imaging and therapy of solid cancer.

  2015cites this paper
• Systems glycobiology for glycoengineering.

  2014cites this paper
• Regulation and function of silayltransferases in pancreatic cancer

  2014cites this paper