Glycosylation in Cancer: Interplay between Multidrug Resistance and Epithelial-to-Mesenchymal Transition?

Fonseca, Leonardo Marques da; Silva, Vanessa Amil da; Freire-de-Lima, Leonardo; Previato, José O.; Capella, Marcia A. M.

doi:10.3389/fonc.2016.00158

Cited by 46 publications

(43 citation statements)

References 130 publications

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“…WGA, a member of the lectin family, selectively binds to N ‑acetylglucosamine and N ‑acetylneuraminic acid (sialic acid) residues found on the surface of cells and WGA staining reveals the heterogeneity of the plasma membrane . With respect to our WGA findings, it has been reported that correlations exist between metastatic behavior, drug resistance, epithelial‐to‐mesenchymal transition, and glycosylation patterns and levels . These results suggest that an important consequence of SET accumulation in normal cells may be cellular transformation.…”

Section: Resultssupporting

confidence: 75%

SET/I2PP2A overexpression induces phenotypic, molecular, and metabolic alterations in an oral keratinocyte cell line

et al. 2017

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The multifunctional SET/I2PP2A protein is known to be overexpressed in head and neck squamous cell carcinoma. However, SET has been reported to have apparently conflicting roles in promoting cancer cell survival under oxidative stress conditions and preventing invasion and metastasis, complicating efforts to understand the contribution of SET to carcinogenesis. In the present study, we overexpressed SETin a spontaneously immortalized oral keratinocyte cell line (NOK-SI SET) and demonstrated that SET upregulation alone was sufficient to transform cells. In comparison with NOK-SI cells, NOK-SI SET cells demonstrated increased levels of phosphorylated Akt, c-Myc and inactive/phosphorylated Rb, together with decreased total Rb protein levels. In addition, NOK-SI SET cells presented the following: (a) a spindle-cell shape morphology compared with the polygonal morphology of NOK-SI cells; (b) loss of mesenchymal stem cell markers CD44 and CD73, and epithelial cell markers CD71 and integrin α6/β4; (c) the ability to form xenograft tumors in nude mice; and (d) increased mitochondrial respiration accompanied by decreased ROSlevels. Overall, our results show that SEToverexpression promotes morphological and oncogenic cell transformation of an oral keratinocyte cell.

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Section: Resultssupporting

confidence: 75%

SET/I2PP2A overexpression induces phenotypic, molecular, and metabolic alterations in an oral keratinocyte cell line

et al. 2017

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“…13,21,24,25 There were also a large number of reports that protein glycosylation modification would alter during the progression of cancer, which played roles in cancer cell signaling, tumor cell dissociation and invasion, cell-matrix interactions, angiogenesis, and metastasis. 26,27 Exploration of the role of EpCAM was also beginning, and few studies have unveiled the involvement of N-glycosylation of EpCAM in breast cancer. In this study, we aimed to understand the role of EpCAM N-glycosylation in the apoptosis process in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

The role of epithelial cell adhesion molecule N-glycosylation on apoptosis in breast cancer cells

Zhang

Gao

et al. 2017

Tumour Biol.

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Glycosylation of cell surface proteins plays an important role in the regulation of apoptosis. It has been demonstrated that knockdown of epithelial cell adhesion molecule promoted apoptosis, inhibited cell proliferation, and caused cell-cycle arrest. In this study, we investigated whether and how N-glycosylation of epithelial cell adhesion molecule influenced the apoptosis in breast cancer cells. We applied the N-glycosylation mutation epithelial cell adhesion molecule plasmid to express deglycosylation of epithelial cell adhesion molecule and then to study its function. Our results showed that deglycosylation of epithelial cell adhesion molecule promoted apoptosis and inhibited cell proliferation. Deglycosylation of epithelial cell adhesion molecule enhanced the cytotoxic effect of 5-fluorouracil, promoting apoptosis by downregulating the expression of the anti-apoptotic protein Bcl-2 and upregulating the expression of the pro-apoptotic proteins Bax and Caspase 3 via the extracellular-signal-regulated kinase 1/2 and c-Jun N-terminal kinase mitogen-activated protein kinase signaling pathways in MCF-7 and MDA-MB-231 cells. These findings are important for a better understanding of epithelial cell adhesion molecule apoptosis regulation and suggest epithelial cell adhesion molecule as a potential target for the treatment of breast cancer.

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“…25,26 To date, one of the most remarkable functions for glycosylation is its role in cell adhesion and migration, specifically in cancer metastasis. [27][28][29][30][31] In addition, glycans have been documented for their role in extracellular matrix (ECM) turnover and remodeling in multiple diseases. [32][33][34] Hence, there is a great need for high-throughput technologies to phenotype clinical diseases using glycoanalytic approaches.…”

Section: Metabolism Glycosylationmentioning

confidence: 99%

Novel Methods in Pulmonary Hypertension Phenotyping in the Age of Precision Medicine (2015 Grover Conference Series)

et al. 2016

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Among pulmonary vascular diseases, pulmonary hypertension (PH) is the best studied and has been the focus of our work. The current classification of PH is based on a relatively simple combination of patient characteristics and hemodynamics. This leads to inherent limitations, including the inability to customize treatment and the lack of clarity from a more granular identification based on individual patient phenotypes. Accurate phenotyping of PH can be used in the clinic to select therapies and determine prognosis and in research to increase the homogeneity of study cohorts. Rapid advances in the mechanistic understanding of the disease, improved imaging methods, and innovative biomarkers now provide an opportunity to define novel PH phenotypes. We have recently shown that altered metabolism may affect nitric oxide levels and protein glycosylation, the peripheral circulation (which may provide insights into the response to therapy), and exhaled-breath analysis (which may be useful in disease evaluation). This review is based on a talk presented during the 2015 Grover Conference and highlights the relevant literature describing novel methods to phenotype pulmonary arterial hypertension patients by using approaches that involve the pulmonary and systemic (peripheral) vasculature. In particular, abnormalities in metabolism, the pulmonary and peripheral circulation, and exhaled breath in PH may help identify phenotypes that can be the basis for a precision-medicine approach to PH management. These approaches may also have a broader scope and may contribute to a better understanding of other diseases, such as asthma, diabetes, and cancer.

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Glycosylation in Cancer: Interplay between Multidrug Resistance and Epithelial-to-Mesenchymal Transition?

Cited by 46 publications

References 130 publications

SET/I2PP2A overexpression induces phenotypic, molecular, and metabolic alterations in an oral keratinocyte cell line

SET/I2PP2A overexpression induces phenotypic, molecular, and metabolic alterations in an oral keratinocyte cell line

The role of epithelial cell adhesion molecule N-glycosylation on apoptosis in breast cancer cells

Novel Methods in Pulmonary Hypertension Phenotyping in the Age of Precision Medicine (2015 Grover Conference Series)

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