Role of Wnt Co-Receptor LRP6 in Triple Negative Breast Cancer Cell Migration and Invasion

Ma, Jinlu; Lü, Wenyan; Chen, Dongquan; Xu, Bo; Li, Yonghe

doi:10.1002/jcb.25956

Cited by 56 publications

(47 citation statements)

References 47 publications

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“…In our own study, we observed a dramatic decrease in the invasive and migrative capacities, along with changes in proliferation and apoptosis of trophoblast cells, after downregulation of LRP6 expression by miR‐590‐3p in HTR‐8/SVneo cells. These findings are consistent with studies in various tumor models (Fan, Shi, Li, & Kuang, ; Jackson et al, ; Ma, Lu, Chen, Xu, & Li, ). For instance, antibody against LRP6 was able to inhibit tumor growth (Jackson et al, ).…”

Section: Discussionsupporting

confidence: 92%

MicroRNA‐590‐3p inhibits trophoblast‐dependent maternal spiral artery remodeling by repressing low‐density lipoprotein receptor‐related protein 6

Zhang

Pan

et al. 2018

Molec Gen & Gen Med

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BackgroundThe remodeling of maternal spiral artery following embryo implantation, which relies on well‐regulated trophoblast functions, is a pivotal process to ensure a successful pregnancy. Low‐density lipoprotein receptor‐related protein 6 (LRP6) and microRNAs (miRNAs, miRs) are suggested to be involved in angiogenesis and several vascular diseases; however, their functions in the control of trophoblast remain elusive. We therefore aimed to examine the roles of LRP6 and miR‐590‐3p in the regulation of trophoblast during the remodeling of maternal spiral artery.MethodsHTR‐8/SVneo cell, a trophoblast cell line, was utilized to study the effects of LRP6 and miR‐590‐3p on apoptosis, cell proliferation, migration, invasion, as well as tube formation. Expression of angiogenic factors placental growth factor (PlGF), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and activities of canonical Wnt/β‐catenin signaling pathway, which were implicated in the process of artery remodeling, were also examined.ResultsMiR‐590‐3p directly targeted 3′ untranslated region (3′‐UTR) of LRP6 mRNA and repressed LRP6 expression, which in turn inhibited proliferation, migration, invasion, as well as tube formation, and resulted in apoptosis in HTR‐8/SVneo cells. Further, inhibition of LRP6 through miR‐590‐3p significantly suppressed the expression of PlGF, MMPs, and VEGF and reduced the activation of Wnt/β‐catenin signaling pathway.ConclusionMicroRNAs‐590‐3p may inhibit trophoblast‐dependent maternal spiral artery remodeling, via both trophoblast invasion and endovascular formation, by repressing LRP6.

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Section: Discussionsupporting

confidence: 92%

MicroRNA‐590‐3p inhibits trophoblast‐dependent maternal spiral artery remodeling by repressing low‐density lipoprotein receptor‐related protein 6

Zhang

Pan

et al. 2018

Molec Gen & Gen Med

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“…Wnt ligands (Wnt10b/3) or receptors (FZD7/LRP6) mediate activation of the β-catenin pathway responsible for EMT induction. 29,[57][58][59][60] In contrast, Wnt5a/5b-induced EMT is not dependent on β-catenin, but is involved in FZD2/STAT3 signaling. 61 Ectopic expression of DKK1/SFRP1 or recombinant DKK1/SFRP1 suppresses breast epithelial cell EMT, further proving the role of Wnt ligands and receptors in this process.…”

Section: Cancer Cell Epith Elial-mesenchymal Transitionmentioning

confidence: 99%

“…Both canonical and noncanonical Wnt pathways are involved in EMT of breast stem cells or cancer cells. Wnt ligands (Wnt10b/3) or receptors (FZD7/LRP6) mediate activation of the β‐catenin pathway responsible for EMT induction . In contrast, Wnt5a/5b‐induced EMT is not dependent on β‐catenin, but is involved in FZD2/STAT3 signaling .…”

Section: Wnt Signaling Induces Breast Cancer Cell Epithelial‐mesenchymentioning

confidence: 99%

Wnt signaling in human and mouse breast cancer: Focusing on Wnt ligands, receptors and antagonists

et al. 2018

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Wnt proteins, a group of secreted glycoproteins, mainly combine with receptors Frizzled (FZD) and/or low‐density‐lipoprotein receptor‐related proteins 5/6 (LRP5/6), initiating β‐catenin‐dependent and ‐independent signaling pathways. These pathways, which can be regulated by some secreted antagonists such as secreted Frizzled‐related proteins (SFRP) and dickkopf‐related protein (DKK), play a critical role in embryo development and adult homeostasis. Overactivation of Wnt signaling has been implicated in some human diseases including cancer. Wnt transgenic mice provide convincing evidence that Wnt signaling is involved in breast cancer initiation and progression, which is further strengthened by observations on human clinical breast cancer patients and studies on in vitro cultured human breast cancer cells. This review focuses on the roles of Wnt ligands, receptors and antagonists in breast cancer development instead of molecules or signaling transactivating β‐catenin independent on Wnt upstream components.

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“…This is consistent with studies showing that the canonical Wnt/β-catenin pathway plays an important role in cellular migration and invasion in multiple tumor types including breast, prostate, gastric, hepatocellular, lung, and thyroid carcinoma cells. 45–51 Pyrvinium has been shown to inhibit β-catenin driven gene transcription, but multiple different mechanisms can inhibit the Wnt/β-catenin pathway including interruption of Wnt interaction with the Frizzled/LRP receptor, 45,46,50 decreasing Wnt ligands, 49 abrogating β-catenin degradation, 51 or altering β-catenin’s interaction with transcription factors in the nucleus affecting gene transcription. 48 This suggests that drug targeting could be tested at a variety of different points in the Wnt/β-catenin signalling cascade making this a fruitful future direction in cancer therapy, including in WT.…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic Inhibition of β-Catenin With Pyrvinium Inhibits Murine and Human Models of Wilms Tumor

et al. 2017

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Wilms tumor (WT) is the most common renal malignancy of childhood and the fourth most common pediatric solid malignancy in the United States. While the mechanisms underlying the WT biology are complex, these tumors most often demonstrate activation of the canonical Wnt/β-catenin pathway. We and others have shown that constitutive activation of β-catenin restricted to the renal epithelium is sufficient to induce primitive renal epithelial tumors which resemble human WT. Here we demonstrate that pharmacologic inhibition of β-catenin gene transcription with pyrvinium inhibits tumor growth and metastatic progression in a murine model of WT. Cellular invasion is significantly inhibited in both murine WT-like and human WT cells and is accompanied by downregulation of the oncogenes Myc and Birc5 (survivin). Our studies provide a proof of concept that the canonical Wnt/β-catenin pathway may be a novel therapeutic target in the management of WT.

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Role of Wnt Co-Receptor LRP6 in Triple Negative Breast Cancer Cell Migration and Invasion

Cited by 56 publications

References 47 publications

MicroRNA‐590‐3p inhibits trophoblast‐dependent maternal spiral artery remodeling by repressing low‐density lipoprotein receptor‐related protein 6

MicroRNA‐590‐3p inhibits trophoblast‐dependent maternal spiral artery remodeling by repressing low‐density lipoprotein receptor‐related protein 6

Wnt signaling in human and mouse breast cancer: Focusing on Wnt ligands, receptors and antagonists

Pharmacologic Inhibition of β-Catenin With Pyrvinium Inhibits Murine and Human Models of Wilms Tumor

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