Redundant expression of canonical Wnt ligands in human breast cancer cell lines

Benhaj, Khemais; Akçalı, Kamil Can; Öztürk, Mehmet

doi:10.3892/or.15.3.701

Cited by 112 publications

(124 citation statements)

References 26 publications

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“…Wnt ligands and FZD receptors are expressed in human breast cancer cell lines and primary tumors (30)(31)(32)(33). Multiple negative regulators of Wnt/β-catenin signaling, such as SFRP1, SFRP2, SFRP5, WIF1, DKK1, and DKK3, are down-regulated in many breast tumors (34)(35)(36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells

Wang

Zhou

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

166

119

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Prodigiosin, a natural red pigment produced by numerous bacterial species, has exhibited promising anticancer activity; however, the molecular mechanisms of action of prodigiosin on malignant cells remain unclear. Aberrant activation of the Wnt/β-catenin signaling cascade is associated with numerous human cancers. In this study, we identified prodigiosin as a potent inhibitor of the Wnt/ β-catenin pathway. Prodigiosin blocked Wnt/β-catenin signaling by targeting multiple sites of this pathway, including the lowdensity lipoprotein-receptor-related protein (LRP) 6, Dishevelled (DVL), and glycogen synthase kinase-3β (GSK3β). In breast cancer MDA-MB-231 and MDA-MB-468 cells, nanomolar concentrations of prodigiosin decreased phosphorylation of LRP6, DVL2, and GSK3β and suppressed β-catenin-stimulated Wnt target gene expression, including expression of cyclin D1. In MDA-MB-231 breast cancer xenografts and MMTV-Wnt1 transgenic mice, administration of prodigiosin slowed tumor progression and reduced the expression of phosphorylated LRP6, phosphorylated and unphosphorylated DVL2, Ser9 phosphorylated GSK3β, active β-catenin, and cyclin D1. Through its ability to inhibit Wnt/β-catenin signaling and reduce cyclin D1 levels, prodigiosin could have therapeutic activity in advanced breast cancers.prodigiosin | Wnt/beta-catenin signaling | breast cancer | LRP6 | Dishevelled (DVL)

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Section: Discussionmentioning

confidence: 99%

Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells

Wang

Zhou

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

166

119

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“…Specifically, we analyzed expression of Wnt10b since it is upregulated in many forms of cancer and because it has been shown to promote hyperplasia and transformation in certain experimental models. [47][48][49][50][51] PCR using primers specific for Wnt10b revealed an average 2.8-fold increase in Wnt10b in samples treated with siRNA duplexes targeting UBE1 compared to control samples (Fig. 5C).…”

Section: Mammalian Cells With Reduced E1 Levels Show Altered Expressimentioning

confidence: 99%

Mutation of the Gene Encoding the Ubiquitin Activating Enzyme Uba1 Causes Tissue Overgrowth in Drosophila

Pfleger¹,

Harvey²,

Yan³

et al. 2007

Fly

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Protein ubiquitination has been shown to regulate a wide variety of cellular process including cell cycle progression, protein trafficking and apoptosis. Most regulation of ubiquitination occurs at the level of E2 or E3 enzymes and their interactions with specific substrates. In a screen for mutations that cause tissue overgrowth, we recovered multiple mutations in the Drosophila Uba1 gene that encodes the E1 enzyme that is required for the first step of most, if not all, ubiquitination reactions. Previous studies with yeast and mammalian cells have shown that disrupting E1 function results in a cell-cycle arrest. Here we show that in the developing Drosophila eye, clones of cells that are homozygous for partial loss of function alleles of Uba1 show defects in apoptosis. Moreover, clones homozygous for stronger or complete loss of function alleles of Uba1, that are predicted to have a global defect on ubiquitination, survive poorly but are able to stimulate the overgrowth of adjacent wild-type tissue. Experiments with mammalian cells show that reducing the level of RNA of the mammalian Uba1 ortholog, UBE1, also results in increased expression of specific growth factor genes. Our studies show that a reduction in E1 activity can promote tissue growth in a multicellular organism and raise the possibility that changes in E1 activity may occur during normal development or in cancer.

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“…Three genes, transcription factor 7 (TCF7), nuclear receptor coactivator 6 (NCOA6), and engrailed-2 (EN2), were identified as putative miR159 targets by all three methods. TCF7 is a TCF/LEF family transcription factor of the Wnt signaling pathway that is upregulated in BC [41,42], is a target of several tumor suppressor miRNAs [43], and can drive BC cell proliferation [44][45][46]. NCOA6 is a transcriptional coactivator that is upregulated in BC [47,48] and may influence a variety of processes including cell growth, development, and wound healing [49].…”

Section: Mir159 Binds To and Targets Transcripts Of Human Tcf7mentioning

confidence: 99%

Cross-kingdom inhibition of breast cancer growth by plant miR159

Fong²,

et al. 2016

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MicroRNAs (miRNAs) are critical regulators of gene expression, and exert extensive impacts on development, physiology, and disease of eukaryotes. A high degree of parallelism is found in the molecular basis of miRNA biogenesis and action in plants and animals. Recent studies interestingly suggest a potential cross-kingdom action of plant-derived miRNAs, through dietary intake, in regulating mammalian gene expression. Although the source and scope of plant miRNAs detected in mammalian specimens remain controversial, these initial studies inspired us to determine whether plant miRNAs can be detected in Western human sera and whether these plant miRNAs are able to influence gene expression and cellular processes related to human diseases such as cancer. Here we found that Western donor sera contained the plant miRNA miR159, whose abundance in the serum was inversely correlated with breast cancer incidence and progression in patients. In human sera, miR159 was predominantly detected in the extracellular vesicles, and was resistant to sodium periodate oxidation suggesting the plant-originated 2'-O-methylation on the 3′ terminal ribose. In breast cancer cells but not non-cancerous mammary epithelial cells, a synthetic mimic of miR159 was capable of inhibiting proliferation by targeting TCF7 that encodes a Wnt signaling transcription factor, leading to a decrease in MYC protein levels. Oral administration of miR159 mimic significantly suppressed the growth of xenograft breast tumors in mice. These results demonstrate for the first time that a plant miRNA can inhibit cancer growth in mammals.

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Redundant expression of canonical Wnt ligands in human breast cancer cell lines

Cited by 112 publications

References 26 publications

Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells

Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells

Mutation of the Gene Encoding the Ubiquitin Activating Enzyme Uba1 Causes Tissue Overgrowth in Drosophila

Cross-kingdom inhibition of breast cancer growth by plant miR159

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