WSB-1 regulates the metastatic potential of hormone receptor negative breast cancer

Poujade, Flore-Anne; Mannion, Aarren J; Brittain, Nicholas; Theodosi, Andrew; Beeby, Ellie; Leszczynska, Katarzyna B.; Hammond, Ester M.; Greenman, John; Cawthorne, Christopher; Pires, Isabel

doi:10.1038/s41416-018-0056-3

Cited by 22 publications

(13 citation statements)

References 29 publications

(50 reference statements)

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“…The present study demonstrated that WSB2 was upregulated in the breast cancer tissue, which was associated with a poor survival in breast cancer. Moreover, WSB2 promotes the migration of McF-7 cells, which was consistent with previous findings; for example, WSB2 exerts a negative regulatory effect on IL-21R expression and signal transduction (27); the knockdown of WSB2 decreased the levels of c-Myc, β-catenin, p-Rb, cdK4 and cyclin d3 in G361 melanoma cells (26); WSB1 knockdown has been shown to be associated with decreased matrix metalloproteinase (MMP) activity (25). However, the mechanisms through which WSB2 regulates breast cancer progression warrant further investigation.…”

Section: Discussionsupporting

confidence: 90%

“…WSB2 contains Wd repeats and a SOcS box, which mediate intracellular signal transduction (24). Its homolog, WSB1, has been reported as an important regulator of aggressive metastasis in hormone receptor-negative breast cancer (25). It has been demonstrated that the expression of WSB2 is higher in human melanoma tissues; consistently, cell cycle progression and migration of A375 and G361 melanoma cells were shown to be significantly inhibited by WSB2 knockdown (26).…”

Section: Discussionmentioning

confidence: 99%

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miR‑28‑5p inhibits the migration of breast�cancer by regulating WSB2

Zhang

2020

Int J Mol Med

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MicroRNAs (miRNAs or miRs) play an important role in the tumorigenesis and progression of breast cancer. However, the function of miR-28-5p in breast cancer migration has yet to be determined. In the present study, Human MicroRNA Expression database (HMEd) analysis revealed that the expression level of miR-28-5p was significantly lower in breast cancer tissue than in normal breast tissue. Kaplan-Meier plotter (KMPLOT) analysis revealed that the low expression level of miR-28-5p was associated with a poor survival in breast cancer. In addition, reverse transcription-quantitative PcR (RT-qPcR) revealed that the expression of miR-28-5p was significantly lower in breast cancer cell lines compared with that in human mammary epithelial cells (HMEcs). Moreover, transfection with miR-28-5p mimics suppressed the migration of McF-7 cells, whereas an miR-28-5p inhibitor exerted the opposite effect. Gene chip assay identified 648 differentially expressed genes (DEGs) in cells overexpressing miR-28-5p. The dEGs are enriched in the 'focal adhesion' and 'pathway in cancer' pathways. The expression levels of Ras-related protein Rap-1b (RAP1B), Wd repeat and SOcS box containing 2 (WSB2) and vascular endothelial growth factor A (VEGFA) were confirmed by RT-qPcR. Furthermore, transfection with miR-28-5p mimics decreased WSB2 expression, whereas the miR-28-5p inhibitor increased the expression of WSB2, at both the transcriptional and translational levels. miR-28-5p targets the 3'UTR of WSB2, and the binding site is conserved in multiple species, with a consensus motif of 5'-AGcUccUU-3'. Moreover, WSB2 overexpression promoted the migration of McF-7 cells which had been inhibited by miR-28-5p. UALcAN analysis revealed that WSB2 was significantly upregulated in primary breast tumor tissue, and a high expression level of WSB2 was associated with a poor survival in breast cancer. Furthermore, immunohistochemistry revealed that the expression of WSB2 was markedly higher in breast cancer tissue compared with that in adjacent normal breast tissue. Taken together, the findings of the present study demonstrate that miR-28-5p inhibits the migration of breast cancer cells by regulating WSB2 expression, and the miR-28-5p/WSB2 axis may be a novel therapeutic target in breast cancer.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

miR‑28‑5p inhibits the migration of breast�cancer by regulating WSB2

Zhang

2020

Int J Mol Med

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“…Whole cell lysates were prepared as previously described (Poujade et al, 2018). Briefly, cells were washed with PBS 1X and detached mechanically.…”

Section: Cell Lysis and Western Blot Analysismentioning

confidence: 99%

Secondary metabolites (essential oils) from sand-dune plants induce cytotoxic effects in cancer cells

Beeby

Magalhães

Poças

et al. 2020

Journal of Ethnopharmacology

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Despite advances in modern therapeutic strategies, cancer remains the second leading cause of death worldwide. Therefore, there is a constant need to develop more efficient anticancer targeting strategies. The anticancer therapeutic proprieties of medicinal plants and their bioactive compounds have been reported for several years, making natural extracts and/or compounds derived from these a promising source of novel anticancer agents. Sand dune plants are subjected to severe environmental stresses, leading to the development of adaptations, including the production of secondary metabolites with a wide range of bioactivities, such as: anti-inflammatory, analgesic, antiseptic, hypoglycaemic, hypotensive, antinociceptive, antioxidant and anticancer. Aim of the study: The anticancer potential of sand dune plants remains under-investigated, so this research describes the characterisation of the composition of bioactive EOs from sand-dune plants of Peniche (Portugal), and assessment of their activity in vitro and potential mechanism of action. Materials and methods: EOs were extracted from six sand-dune species of plants from Peniche sand dunes: Crithmum maritimum L., Seseli tortuosum L., Artemisia campestris subsp. maritima (DC.) Arcang., Juniperus phoenicea var. turbinata (Guss.) Parl., Otanthus maritimus (L.) Hoffmanns. & Link, and Eryngium maritimum L.. EOs composition was fully characterised chemically using Gas Chromatography-Mass Spectrometry (GC-MS). The assessment of anticancer activity and mechanism of action was performed in vitro using breast and colorectal cancer 2D and 3D spheroid cell line models, through cell proliferation assay, western blotting analysis, and cell cycle analysis. Results: EOs from the majority of the species tested (S. tortuosum, A. campestris subsp. maritima, O. maritimus, and E. maritimum) were mainly composed by hydrocarbon compounds (sequisterpenes and monoterpenes), showing antiproliferative activity in both 2D and 3D models. EO extracted from S. tortuosum and O. maritimus were identified as having the lowest IC 50 values for both cell lines when compared with the other species tested. Furthermore, this antiproliferative activity was associated with increased p21 expression and induction of apoptosis. Conclusions: The present study suggests that EOs extracted from S. tortuosum and O. maritimus present promising cytotoxic properties. Further evaluation of the extracts and their key components as potential anticancer agents should therefore be explored.

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“…Metastatic breast cancer, which has high metastatic potential to other organs in the body, is of major concern as a causal factor for cancer death in women. [28][29][30] Recent studies have indicated that the aggressive and highly metastatic characteristics of breast cancer are, in part, associated with the aberrant methylation of histone H3 lysine 79 (H3K79me2) mediated by a histone methyltransferase, DOT1L. 18 Therefore, approaches to developing inhibitors for DOT1L in breast cancer are actively being studied.…”

Section: Discussionmentioning

confidence: 99%

Targeting Histone Methyltransferase DOT1L by a Novel Psammaplin A Analog Inhibits Growth and Metastasis of Triple-Negative Breast Cancer

Byun

Kim

Han

et al. 2019

Molecular Therapy - Oncolytics

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Triple-negative breast cancer (TNBC) is the most intractable cancer in women with a high risk of metastasis. While hyper-methylation of histone H3 catalyzed by disruptor of telomeric silencing 1-like (DOT1L), a specific methyltransferase for histone H3 at lysine residue 79 (H3K79), is reported as a potential target for TNBCs, early developed nucleoside-type DOT1L inhibitors are not sufficient for effective inhibition of growth and metastasis of TNBC cells. We found that TNBC cells had a high expression level of DOT1L and a low expression level of E-cadherin compared to normal breast epithelial cells and non-TNBC cells. Here, a novel psammaplin A analog (PsA-3091) exhibited a potent inhibitory effect of DOT1L-mediated H3K79 methylation. Consistently, PsA-3091 also significantly inhibited the proliferation, migration, and invasion of TNBC cells along with the augmented expression of E-cadherin and the suppression of N-cadherin, ZEB1, and vimentin expression. In an orthotopic mouse model, PsA-3091 effectively inhibited lung metastasis and tumor growth by the regulation of DOT1L activity and EMT biomarkers. Together, we report here a new template of DOT1L inhibitor and suggest that targeting DOT1L-mediated H3K79 methylation by a novel PsA analog may be a promising strategy for the treatment of metastatic breast cancer patients.

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WSB-1 regulates the metastatic potential of hormone receptor negative breast cancer

Abstract: Our data suggests that WSB-1 may be an important regulator of aggressive metastatic disease in hormone receptor-negative breast cancer. WSB-1 could therefore represent a novel regulator and therapeutic target for secondary breast cancer in these patients.

Cited by 22 publications

References 29 publications

miR‑28‑5p inhibits the migration of breast�cancer by regulating WSB2

miR‑28‑5p inhibits the migration of breast�cancer by regulating WSB2

Secondary metabolites (essential oils) from sand-dune plants induce cytotoxic effects in cancer cells

Targeting Histone Methyltransferase DOT1L by a Novel Psammaplin A Analog Inhibits Growth and Metastasis of Triple-Negative Breast Cancer

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