Vitamin D compounds inhibit cancer stem-like cells and induce differentiation in triple negative breast cancer

Shan, Naing Lin; Wahler, J.; Lee, Hong Jin; Bak, Min Ji; Gupta, Saurabh; Maehr, Hubert; Suh, Nanjoo

doi:10.1016/j.jsbmb.2016.12.001

Cited by 64 publications

(36 citation statements)

References 49 publications

(55 reference statements)

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“…Inhibition of Notch ligands and of other genes belonging to the Notch pathway (Additional File 4) suggests a differentiating effect of vitamin D on these cells. Interestingly, inhibition of Notch-signalling molecules, which play a role in cancer stem cell maintenance, is one of the mechanisms that mediate the anticancer properties of vitamin D (So & Suh, 2015;Shan et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Vitamins D3 and D2 have marked but different global effects on gene expression in a rat oligodendrocyte precursor cell line

Mengozzi

Hesketh

Bucca

et al. 2020

Mol Med

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Background: Vitamin D deficiency increases the risk of developing multiple sclerosis (MS) but it is unclear whether vitamin D supplementation improves the clinical course of MS, and there is uncertainty about the dose and form of vitamin D (D2 or D3) to be used. The mechanisms underlying the effects of vitamin D in MS are not clear. Vitamin D3 increases the rate of differentiation of primary oligodendrocyte precursor cells (OPCs), suggesting that it might help remyelination in addition to modulating the immune response. Here we analyzed the transcriptome of differentiating rat CG4 OPCs treated with vitamin D2 or with vitamin D3 at 24 h and 72 h following onset of differentiation. Methods: Gene expression in differentiating CG4 cells in response to vitamin D2 or D3 was quantified using Agilent DNA microarrays (n = 4 replicates), and the transcriptome data were processed and analysed using the R software environment. Differential expression between the experimental conditions was determined using LIMMA, applying the Benjamini and Hochberg multiple testing correction to p-values, and significant genes were grouped into coexpression clusters by hierarchical clustering. The functional significance of gene groups was explored by pathway enrichment analysis using the clusterProfiler package. Results: Differentiation alone changed the expression of about 10% of the genes at 72 h compared to 24 h. Vitamin D2 and D3 exerted different effects on gene expression, with D3 influencing 1272 genes and D2 574 at 24 h. The expression of the vast majority of these genes was either not changed in differentiating cells not exposed to vitamin D or followed the same trajectory as the latter. D3-repressed genes were enriched for Gene Ontology (GO) categories including transcription factors and the Notch pathway, while D3-induced genes were enriched for the Ras pathway. Conclusions: This study shows that vitamin D3, compared with D2, changes the expression of a larger number of genes in OLs. Identification of genes affected by D3 in OLs should help to identify mechanisms mediating its action in MS.

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Section: Discussionmentioning

confidence: 99%

Vitamins D3 and D2 have marked but different global effects on gene expression in a rat oligodendrocyte precursor cell line

Mengozzi

Hesketh

Bucca

et al. 2020

Mol Med

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“…Given the role of cholesterol in the RBC membrane, it is plausible that cholesterol regulates cell survival. However, the function of the CSP might not be limited to cell death or stress mechanisms because previously published work has indicated a regulatory function for cholesterol and its derivatives at the level of cellular differentiation [53][54][55][56][57][58][59][60] . Future work that analyzes both primitive and definitive hematopoiesis at unique stages of differentiation in different model systems is likely to identify the exact cellular mechanisms underlying the phenotypic alteration we describe.…”

Section: Discussionmentioning

confidence: 99%

Mutations in the zebrafishhmgcs1gene reveal a novel function for isoprenoids during red blood cell development

Hernández

Castro

Reyes-Nava

et al. 2018

Preprint

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word count: 187 Number of figures and tables: 5 Number of references: 72 Key Points 1. The products of the cholesterol synthesis pathway regulate red blood cell development during primitive erythropoiesis. 2. Isoprenoids regulate erythropoiesis by modulating the expression of the GATA1 transcription factor. AbstractErythropoiesis is the process by which new red blood cells (RBCs) are formed and defects in this process can lead to anemia or thalassemia. The GATA1 transcription factor is an established mediator of RBC development. However, the upstream mechanisms that regulate the expression of GATA1 are not completely characterized. Cholesterol is one potential upstream mediator of GATA1 expression because previously published studies suggest that defects in cholesterol synthesis disrupt RBC differentiation. Here we characterize RBC development in a zebrafish harboring a single missense mutation in the hmgcs1 gene (Vu57 allele). hmgcs1 encodes the first enzyme in the cholesterol synthesis pathway and mutation of hmgcs1 inhibits cholesterol synthesis. We analyzed the number of RBCs in hmgcs1 mutants and their wildtype siblings. Mutation of hmgcs1 resulted in a decrease in the number of mature RBCs, which coincides with reduced gata1a expression. We combined these experiments with pharmacological inhibition and confirmed that cholesterol and isoprenoid synthesis are essential for RBC differentiation, but that gata1a expression is isoprenoid dependent. Collectively, our results reveal two novel upstream regulators of RBC development and suggest that appropriate cholesterol homeostasis is critical for primitive erythropoiesis.

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“…Interestingly, inhibition of Notch-signalling molecules, which play a role in cancer stem cell maintenance, is one of the mechanisms that mediate the anticancer properties of vitamin D 35,36 .…”

Section: Functional Enrichment Analysis Of the Genes Uniquely Down-rementioning

confidence: 99%

Vitamins D3 and D2 have marked but different global effects on gene expression in a rat oligodendrocyte precursor cell line

Mengozzi

Hesketh

Bucca

et al. 2019

Preprint

View full text Add to dashboard Cite

AbstractVitamin D deficiency increases the risk of developing multiple sclerosis (MS) but there is uncertainty about what dose and form of vitamin D could improve the clinical course of MS. The mechanisms underlying the effects of vitamin D in MS are not clear. Vitamin D3 increases the rate of differentiation of primary oligodendrocyte precursor cells (OPCs), suggesting that it might help remyelination in addition to modulating the immune response. Here we analyzed the transcriptome of differentiating rat CG4 OPCs treated with vitamin D2 or with D3 at 24 h and 72 h following onset of differentiation. Differentiation alone changed the expression of about 10% of the genes at 72 h compared to 24 h. Vitamin D2 and D3 exerted different effects on gene expression, with D3 influencing 1,272 genes and D2 574 at 24 h. The expression of the vast majority of these genes was either not changed in differentiating cells not exposed to vitamin D or followed the same trajectory as the latter. D3-repressed genes were enriched for gene ontology categories including transcription factors and the Notch pathway, while D3-induced genes were enriched for the Ras pathway. These findings should help to identify mechanisms mediating D3 action in MS.

show abstract

Vitamin D compounds inhibit cancer stem-like cells and induce differentiation in triple negative breast cancer

Cited by 64 publications

References 49 publications

Vitamins D3 and D2 have marked but different global effects on gene expression in a rat oligodendrocyte precursor cell line

Vitamins D3 and D2 have marked but different global effects on gene expression in a rat oligodendrocyte precursor cell line

Mutations in the zebrafishhmgcs1gene reveal a novel function for isoprenoids during red blood cell development

Vitamins D3 and D2 have marked but different global effects on gene expression in a rat oligodendrocyte precursor cell line

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