Sweets for a Bitter End: Lung Cancer Cell–Surface Protein Glycosylation Mediates Metastatic Colonization

Arnal-Estapé, Anna; Nguyen, Don X.

doi:10.1158/2159-8290.cd-15-0013

Cited by 14 publications

(10 citation statements)

References 10 publications

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“…30,31 Different levels of expression of glycans on the surface of cancer cells have caused differences in their metastasis. 32,33 Numerous studies on glycoproteins, especially α2, 6-linked Sias, have shown that the survival rate of cancer patients and their prognosis are closely related to this glycoprotein. 33 Therefore, with sufficient information about the properties of glycan epitopes, it can be used to target proteins and glycans.…”

Section: Discussionmentioning

confidence: 99%

Targeting Mitochondrial-Nuclear Apoptotic Signaling Pathways, Metabolic Pathways and Reversal of Doxorubicin (DOX) Cell Resistance in MCF-7 and MDA‑MB-231 Cancer Cell Lines by Sambucus Nigra (SNA)

Ghanbari¹,

Roshankhah²,

Salahshoor³

et al. 2022

Arch Breast Cancer

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Background: The study aimed to assess the effect of anti-tumor and anti-proliferative properties of Sambucus nigra (SNA) on MCF-7 and MDA MB-231 breast tumor cell lines.Methods: The cytotoxicity of SNA was assessed based on dose/time by the MTT assay. Also, the influence of SNA on apoptotic pathways, cellular and metabolic resistance in these cell lines was examined by real-time PCR, lipid peroxidase was measured by malondialdehyde (MDA) and the effect of apoptosis and necrosis was determined by flow cytometry.Results: Our data showed that DOX, SNA, and DOX + SNA treatment induced the expression of p53, Bax, Bcl-2, Caspase-3, and 8 levels involved in the apoptotic pathways. ATP binding cassette subfamily B member 4 (ABCB4) gene expression was decreased in MDA‑MB-231 breast cancer cells compared to MCF-7. Also, we observed that DOX, SNA, and DOX + SNA treatment induced expression of Monocarboxylate transporters (MCTs) metabolic pathways such as MCT1 and MCT4. Conclusion: Overall, the outcomes of this investigation show that the combination of SNA-Doxorubicin (DOX) in different groups of these cancer cells, especially in the MDA‑MB-231 cell lines synergistically intensified the induction of apoptosis in them. SNA enhances the anti-cancer effects of DOX to induce cellular apoptosis, alter metabolic pathways, and reduce cellular resistance. The research highlights the promising use of SNA as a chemosensitizer in the chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Targeting Mitochondrial-Nuclear Apoptotic Signaling Pathways, Metabolic Pathways and Reversal of Doxorubicin (DOX) Cell Resistance in MCF-7 and MDA‑MB-231 Cancer Cell Lines by Sambucus Nigra (SNA)

Ghanbari¹,

Roshankhah²,

Salahshoor³

et al. 2022

Arch Breast Cancer

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“…Differential surface expression of glycans helps cancer cells in gaining invasive advantage. 42 , 43 Evidences suggest, increase in the endogenous levels of sialylated glycoproteins especially α 2,6-linked Sias, correlate with poor prognosis and survival rate of carcinoma patients. 44 , 45 This unique profile of glycan epitopes can thus be used as ideal candidates to be targeted by specific bait proteins, lectins.…”

Section: Discussionmentioning

confidence: 99%

“…Complex network of sugar residues (glycocalyx) comprises a major part of the ECM, mediating various social events like cellular adhesion, motility and signaling. 4 Although recent advancement of glycomics reportedly link aberrant glycosylation with cancer progression 4 , 5 , 6 , 7 , 8 , 9 albeit necessary insights emphasizing its importance in the perspective of progression of OC are still not available.…”

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confidence: 99%

Targeted apoptosis in ovarian cancer cells through mitochondrial dysfunction in response to Sambucus nigra agglutinin

et al. 2017

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Ovarian carcinoma (OC) patients encounter the severe challenge of clinical management owing to lack of screening measures, chemoresistance and finally dearth of non-toxic therapeutics. Cancer cells deploy various defense strategies to sustain the tumor microenvironment, among which deregulated apoptosis remains a versatile promoter of cancer progression. Although recent research has focused on identifying agents capable of inducing apoptosis in cancer cells, yet molecules efficiently breaching their survival advantage are yet to be classified. Here we identify lectin, Sambucus nigra agglutinin (SNA) to exhibit selectivity towards identifying OC by virtue of its specific recognition of α-2, 6-linked sialic acids. Superficial binding of SNA to the OC cells confirm the hyper-sialylated status of the disease. Further, SNA activates the signaling pathways of AKT and ERK1/2, which eventually promotes de-phosphorylation of dynamin-related protein-1 (Drp-1). Upon its translocation to the mitochondrial fission loci Drp-1 mediates the central role of switch in the mitochondrial phenotype to attain fragmented morphology. We confirmed mitochondrial outer membrane permeabilization resulting in ROS generation and cytochrome-c release into the cytosol. SNA response resulted in an allied shift of the bioenergetics profile from Warburg phenotype to elevated mitochondrial oxidative phosphorylation, altogether highlighting the involvement of mitochondrial dysfunction in restraining cancer progression. Inability to replenish the SNA-induced energy crunch of the proliferating cancer cells on the event of perturbed respiratory outcome resulted in cell cycle arrest before G2/M phase. Our findings position SNA at a crucial juncture where it proves to be a promising candidate for impeding progression of OC. Altogether we unveil the novel aspect of identifying natural molecules harboring the inherent capability of targeting mitochondrial structural dynamics, to hold the future for developing non-toxic therapeutics for treating OC.

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“…The upregulation of sialic acid sugars attached to glycoproteins and glycolipids has become a hallmark of several tumor cell types [331]. As metastasis and invasion depend on extracellular matrix (ECM) molecules like ECM cytokines, growth factors, and cell surface proteins, their altered glycosylation has been shown to induce contact-dependent mechanisms that allow tumor cell extravasation [332]. Specifically, gliomas, which are challenging due to their invasiveness [333], bind hyaluronic acid-based ECM to interact with the lectican family chondroitin sulfate proteoglycans and CD44 [334,335] that are involved in tumor migration.…”

Section: Glycomics and Glycoproteomics In Cancer Studiesmentioning

confidence: 99%

Glycomic and Glycoproteomic Techniques in Neurodegenerative Disorders and Neurotrauma: Towards Personalized Markers

Kobeissy

Kobaisi

Peng

et al. 2022

Cells

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The proteome represents all the proteins expressed by a genome, a cell, a tissue, or an organism at any given time under defined physiological or pathological circumstances. Proteomic analysis has provided unparalleled opportunities for the discovery of expression patterns of proteins in a biological system, yielding precise and inclusive data about the system. Advances in the proteomics field opened the door to wider knowledge of the mechanisms underlying various post-translational modifications (PTMs) of proteins, including glycosylation. As of yet, the role of most of these PTMs remains unidentified. In this state-of-the-art review, we present a synopsis of glycosylation processes and the pathophysiological conditions that might ensue secondary to glycosylation shortcomings. The dynamics of protein glycosylation, a crucial mechanism that allows gene and pathway regulation, is described. We also explain how—at a biomolecular level—mutations in glycosylation-related genes may lead to neuropsychiatric manifestations and neurodegenerative disorders. We then analyze the shortcomings of glycoproteomic studies, putting into perspective their downfalls and the different advanced enrichment techniques that emanated to overcome some of these challenges. Furthermore, we summarize studies tackling the association between glycosylation and neuropsychiatric disorders and explore glycoproteomic changes in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington disease, multiple sclerosis, and amyotrophic lateral sclerosis. We finally conclude with the role of glycomics in the area of traumatic brain injury (TBI) and provide perspectives on the clinical application of glycoproteomics as potential diagnostic tools and their application in personalized medicine.

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Sweets for a Bitter End: Lung Cancer Cell–Surface Protein Glycosylation Mediates Metastatic Colonization

Cited by 14 publications

References 10 publications

Targeting Mitochondrial-Nuclear Apoptotic Signaling Pathways, Metabolic Pathways and Reversal of Doxorubicin (DOX) Cell Resistance in MCF-7 and MDA‑MB-231 Cancer Cell Lines by Sambucus Nigra (SNA)

Targeting Mitochondrial-Nuclear Apoptotic Signaling Pathways, Metabolic Pathways and Reversal of Doxorubicin (DOX) Cell Resistance in MCF-7 and MDA‑MB-231 Cancer Cell Lines by Sambucus Nigra (SNA)

Targeted apoptosis in ovarian cancer cells through mitochondrial dysfunction in response to Sambucus nigra agglutinin

Glycomic and Glycoproteomic Techniques in Neurodegenerative Disorders and Neurotrauma: Towards Personalized Markers

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