Na/K-ATPase: Their role in cell adhesion and migration in cancer

Silva, Camila Ignácio da; Gonçalves-de-Albuquerque, Cassiano Felippe; Moraes, Bianca Portugal Tavares de; Garcia, Diogo Gomes; Burth, Patrícia

doi:10.1016/j.biochi.2021.03.002

Cited by 24 publications

(11 citation statements)

References 86 publications

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“…Conversely, β-escin and horse chestnut seed extract have been tested in clinical trials and are well tolerated in patients. Currently, β-escin is used as an anti-inflammatory, anti-edematous, antioxidant, antiseptic, analgesic, antipyretic, and anti-hemorrhoidal agent [41,42]. The results of our study indicate that β-escin could be a new, cost-effective, and readily available preventative and therapeutic agent for OvCa patients.…”

Section: Discussionmentioning

confidence: 67%

“…In addition, the ability of β-escin to inhibit OvCa cell adhesion in vitro in the present study may be explained, in part, through its inhibition of Na + ,K + -ATPase, which acts as a cell adhesion molecule in adherens junctions. This inhibitory effect is associated with Na + ,K + -ATPase's ability to promote cancer cell adhesion and motility [42]. However, further investigation is needed to link Na + ,K + -ATPase activity with cancer cell adhesion and/or invasion, as well as to determine the effect of β-escin on Na + ,K + -ATPase-dependent processes.…”

Section: Discussionmentioning

confidence: 99%

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The Natural Product β-Escin Targets Cancer and Stromal Cells of the Tumor Microenvironment to Inhibit Ovarian Cancer Metastasis

Kenny

Hart

Kordylewicz

et al. 2021

Cancers

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The high mortality of OvCa is caused by the wide dissemination of cancer within the abdominal cavity. OvCa cells metastasize to the peritoneum, which is covered by mesothelial cells, and invade into the underlying stroma, composed of extracellular matrices (ECM) and stromal cells. In a study using a three-dimensional quantitative high-throughput screening platform (3D-qHTS), we found that β-escin, a component of horse chestnut seed extract, inhibited OvCa adhesion/invasion. Here, we determine whether β-escin and structurally similar compounds have a therapeutic potential against OvCa metastasis. Different sources of β-escin and horse chestnut seed extract inhibited OvCa cell adhesion/invasion, both in vitro and in vivo. From a collection of 160 structurally similar compounds to β-escin, we found that cardiac glycosides inhibited OvCa cell adhesion/invasion and proliferation in vitro, and inhibited adhesion/invasion and metastasis in vivo. Mechanistically, β-escin and the cardiac glycosides inhibited ECM production in mesothelial cells and fibroblasts. The oral administration of β-escin inhibited metastasis in both OvCa prevention and intervention mouse models. Specifically, β-escin inhibited ECM production in the omental tumors. Additionally, the production of HIF1α-targeted proteins, lactate dehydrogenase A, and hexokinase 2 in omental tumors was blocked by β-escin. This study reveals that the natural compound β-escin has a therapeutic potential because of its ability to prevent OvCa dissemination by targeting both cancer and stromal cells in the OvCa tumor microenvironment.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

The Natural Product β-Escin Targets Cancer and Stromal Cells of the Tumor Microenvironment to Inhibit Ovarian Cancer Metastasis

Kenny

Hart

Kordylewicz

et al. 2021

Cancers

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“…Furthermore, these pathways have been shown to promote cancer development and are related to the α and β subunits of Na + /K + -ATPase (30). Among them, the β-subunit potentially plays an important role in the suppression of cancer tumorigenesis and metastasis (31). To study the potential mechanism of ATP1B1 in DLBCL, we analyzed the co-expressed genes of ATP1B1 and found that ATP1B1 is mainly involved in information adhesion, olfactory transduction, CCRI, and extracellular matrixreceptor (ECM receptor) interaction.…”

Section: Discussionmentioning

confidence: 99%

Identification of ATP1B1, a key copy number driver gene in diffuse large B-cell lymphoma and potential target for drugs

Zhang¹,

Wang²,

Liu³

2022

Ann Transl Med

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Background: Copy number variations (CNVs) participate in the development and progression of cancer by altering the expression levels of genes. However, it is unclear whether this correlation exists in diffuse large B-cell lymphoma (DLBCL).Methods: Differentially expressed genes (DEGs) were identified from the GSE25638 and GSE56315 datasets. Modules that were highly related to DLBCL prognosis were obtained by Weighted Gene Coexpression Network Analysis (WGCNA). We performed an integrated analysis between CNV and differential gene expression in The Cancer Genome Atlas (TCGA) DLBCL. The DEGs were then overlapped with the module genes and expression-copy number variations-related (Exp-CNV-related) genes to obtain the common key genes. Time-dependent receiver operating characteristic (ROC) analysis was utilized to evaluate the accuracy of the key gene in predicting the prognosis of DLBCL. Next, we conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to explore the key gene. The potential molecule drugs of the key gene were identified by Connectivity Map (Cmap) analysis.Results: A turquoise module with 160 genes was identified as the signature module. ATP1B1 is overexpressed in DLBCL cell lines, compared to Cluster of Differentiation 19+B (CD19+B) cells. The ROC curve indicated that ATP1B1 could be a biomarker for diagnosing DLBCL, and the forest map suggested that ATP1B1 gene expression levels had a greater impact on the prognosis of patients with DLBCL. The area under curve (AUC) value of the time-dependent ROC curve with values based on the 1-, 3-, and 5-year survivability were 0.576, 0.663, and 0.706, respectively. Pathway analysis demonstrated the relationship between ATP1B1 and focal adhesion, etc. The inhibitory effects of ATP1B1 downregulation on DLBCL cell proliferation, cell migration, invasion, and cell adhesion were also examined. We found out that the higher proliferation ability in ATP1B1-overexpression cells was rescued with roxithromycin.Conclusions: ATP1B1 is a copy number driver gene that could potentially be adopted as a diagnostic biomarker and therapeutic target of DLBCL.

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“…These effects could be very useful in management of cystinosis, which shows inflammasome activation and high ROS production [ 52 , 53 ]. Digoxin is one of the oldest cardiovascular medications used today to manage heart failure, it reversibly inhibits the Na-K ATPase, which has been shown to play a critical role in cell adhesion [ 54 ], and it may block autosis [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Drug Repurposing in Rare Diseases: An Integrative Study of Drug Screening and Transcriptomic Analysis in Nephropathic Cystinosis

Bellomo

Leo

Taranta

et al. 2021

IJMS

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Diagnosis and cure for rare diseases represent a great challenge for the scientific community who often comes up against the complexity and heterogeneity of clinical picture associated to a high cost and time-consuming drug development processes. Here we show a drug repurposing strategy applied to nephropathic cystinosis, a rare inherited disorder belonging to the lysosomal storage diseases. This approach consists in combining mechanism-based and cell-based screenings, coupled with an affordable computational analysis, which could result very useful to predict therapeutic responses at both molecular and system levels. Then, we identified potential drugs and metabolic pathways relevant for the pathophysiology of nephropathic cystinosis by comparing gene-expression signature of drugs that share common mechanisms of action or that involve similar pathways with the disease gene-expression signature achieved with RNA-seq.

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Na/K-ATPase: Their role in cell adhesion and migration in cancer

Cited by 24 publications

References 86 publications

The Natural Product β-Escin Targets Cancer and Stromal Cells of the Tumor Microenvironment to Inhibit Ovarian Cancer Metastasis

The Natural Product β-Escin Targets Cancer and Stromal Cells of the Tumor Microenvironment to Inhibit Ovarian Cancer Metastasis

Identification of ATP1B1, a key copy number driver gene in diffuse large B-cell lymphoma and potential target for drugs

Drug Repurposing in Rare Diseases: An Integrative Study of Drug Screening and Transcriptomic Analysis in Nephropathic Cystinosis

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