Deciphering the Importance of Glycosphingolipids on Cellular and Molecular Mechanisms Associated with Epithelial-to-Mesenchymal Transition in Cancer

Cumin, Cécile; Huang, Yen‐Lin; Everest‐Dass, Arun; Jacob, Francis

doi:10.3390/biom11010062

Cited by 35 publications

(29 citation statements)

References 137 publications

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“…Gangliosides, including GM3, GM2, GM1, and GD1, etc., are a large category of molecules that are widely expressed on many normal human tissues and mediate multiple biological functions. 39 GD2 has been considered an attractive tumor antigen and target for NB cancer therapy. 40 GD2 is abundantly expressed on a wide range of tumors, such as almost all neuroblastomas, most melanomas and retinoblastomas, and gliomas.…”

Section: Discussionmentioning

confidence: 99%

A Novel pH-Sensitive Multifunctional DNA Nanomedicine: An Enhanced and Harmless GD2 Aptamer-Mediated Strategy for Guiding Neuroblastoma Antitumor Therapy

Zhang¹,

Wang²,

Zhu³

et al. 2021

IJN

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Background: GD2 is a mainstream biomarker for neuroblastoma (NB)-targeted therapy. Current anti-GD2 therapeutics exhibit several side effects since GD2 is also expressed at low levels on normal cells. Thus, current anti-GD2 therapeutics can be compromised by the coexistence of the target receptor on both cancer cells and normal cells. Propose: Aptamers are promising and invaluable molecular tools. Because of the pH difference between tumor and normal cells, in this study, we constructed a pH-sensitive aptamer-mediated drug delivery system (IGD-Targeted). Methods: In vivo Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was used to generate a novel GD2 aptamer. Flow cytometry and molecular docking were applied to assess the binding specificities, affinities abilities of the aptamers. Confocal microscope, CCK8 assay, and BrdU assay were utilized to evaluate whether IGD-Targeted could only bind with GD2 at acidic environment. To evaluate whether IGD-Targeted could inhibit GD2-positive tumor and protect normal cells, in vivo living imaging, histomorphological staining, blood test, and RNA-sequencing were observed in animal model. Results: GD2 aptamer termed as DB67 could bind with GD2-positive cells with high specificity, while has minimal cross-reactivities to other negative cells. It has been validated that the i-motif in IGD-Targeted facilitates the binding specificity and affinity of the GD2 aptamer to GD2-positive NB tumor cells but does not interfere with GD2-positive normal cells at the pH of the cellular microenvironment. In addition, IGD-Targeted is capable of delivering Dox to only GD2-positive NB tumor cells and not to normal cells in vivo and in vitro, resulting in precise inhibition of tumor cells and protection of normal cells. Conclusion:This study suggests that IGD-Targeted as a promising platform for NB therapy which could show greater tumor inhibition and fewer side effects to normal cells, regardless of the existence of the same receptor on the target and nontarget cells.

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Section: Discussionmentioning

confidence: 99%

A Novel pH-Sensitive Multifunctional DNA Nanomedicine: An Enhanced and Harmless GD2 Aptamer-Mediated Strategy for Guiding Neuroblastoma Antitumor Therapy

Zhang¹,

Wang²,

Zhu³

et al. 2021

IJN

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“…In addition, EMT has been related to different cancer functions, especially for tumor invasion and metastasis, tumor stemness and resistance to therapy (66). Correspondingly, the resulting mesenchymal cells after migration also can reverse the process, known as mesenchymal-to-epithelial transition (MET), transforming epithelial cells to colonize a particular location (67).…”

Section: The Emt Processmentioning

confidence: 99%

Resveratrol and Its Analogs: Potent Agents to Reverse Epithelial-to-Mesenchymal Transition in Tumors

et al. 2021

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Epithelial-to-mesenchymal transition (EMT), a complicated program through which polarized epithelial cells acquire motile mesothelial traits, is regulated by tumor microenvironment. EMT is involved in tumor progression, invasion and metastasis via reconstructing the cytoskeleton and degrading the tumor basement membrane. Accumulating evidence shows that resveratrol, as a non-flavonoid polyphenol, can reverse EMT and inhibit invasion and migration of human tumors via diverse mechanisms and signaling pathways. In the present review, we will summarize the detailed mechanisms and pathways by which resveratrol and its analogs (e.g. Triacetyl resveratrol, 3,5,4’-Trimethoxystilbene) might regulate the EMT process in cancer cells to better understand their potential as novel anti-tumor agents. Resveratrol can also reverse chemoresistance via EMT inhibition and improvement of the antiproliferative effects of conventional treatments. Therefore, resveratrol and its analogs have the potential to become novel adjunctive agents to inhibit cancer metastasis, which might be partly related to their blocking of the EMT process.

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“…They are implicated in several events related with membrane integrity and cellular interactions. In cancer cells, they are involved in cell proliferation, cell migration, chemoresistance, EMT, metastasis, reduced apoptosis and poor cell differentiation [ 9 , 10 ]. Interestingly, CRC tissues have shown an increased fucosylation and sialylation accompanied by low acetylation and sulfation of glycosphingolipid glycans ( Table 2 ) [ 10 , 100 ].…”

Section: Glycosylated Molecules In Colorectal Cancermentioning

confidence: 99%

“…Proteins can be N-glycosylated and O-glycosylated and these variations determine, in part, their physical and functional properties. The considerable weight of lipid glycosylation in biology has also been demonstrated [ 9 , 10 , 11 ]. As the amount and glycosyltransferase profile could be different depending on the cell type, glycoconjugates can also be dissimilar.…”

Section: Introductionmentioning

confidence: 99%

The Role of Glycosyltransferases in Colorectal Cancer

Fernández-Ponce

Geribaldi-Doldán

Sánchez-Gomar

et al. 2021

IJMS

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Post-translational modifications (PTMs) have been extensively studied in malignancies due to its relevance in tumor pathogenesis and therapy. This review is focused on the dysregulation of glycosyltransferase expression in CRC and its impact in cell function and in several biological pathways associated with CRC pathogenesis, prognosis and therapeutic approaches. Glycan structures act as interface molecules between cells and their environment and in several cases facilitate molecule function. CRC tissue shows alterations in glycan structures decorating molecules, such as annexin-1, mucins, heat shock protein 90 (Hsp90), β1 integrin, carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR), insulin-like growth factor-binding protein 3 (IGFBP3), transforming growth factor beta (TGF-β) receptors, Fas (CD95), PD-L1, decorin, sorbin and SH3 domain-containing protein 1 (SORBS1), CD147 and glycosphingolipids. All of these are described as key molecules in oncogenesis and metastasis. Therefore, glycosylation in CRC can affect cell migration, cell–cell adhesion, actin polymerization, mitosis, cell membrane repair, apoptosis, cell differentiation, stemness regulation, intestinal mucosal barrier integrity, immune system regulation, T cell polarization and gut microbiota composition; all such functions are associated with the prognosis and evolution of the disease. According to these findings, multiple strategies have been evaluated to alter oligosaccharide processing and to modify glycoconjugate structures in order to control CRC progression and prevent metastasis. Additionally, immunotherapy approaches have contemplated the use of neo-antigens, generated by altered glycosylation, as targets for tumor-specific T cells or engineered CAR (Chimeric antigen receptors) T cells.

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Deciphering the Importance of Glycosphingolipids on Cellular and Molecular Mechanisms Associated with Epithelial-to-Mesenchymal Transition in Cancer

Cited by 35 publications

References 137 publications

A Novel pH-Sensitive Multifunctional DNA Nanomedicine: An Enhanced and Harmless GD2 Aptamer-Mediated Strategy for Guiding Neuroblastoma Antitumor Therapy

A Novel pH-Sensitive Multifunctional DNA Nanomedicine: An Enhanced and Harmless GD2 Aptamer-Mediated Strategy for Guiding Neuroblastoma Antitumor Therapy

Resveratrol and Its Analogs: Potent Agents to Reverse Epithelial-to-Mesenchymal Transition in Tumors

The Role of Glycosyltransferases in Colorectal Cancer

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