GPR48 Promotes Multiple Cancer Cell Proliferation via Activation of Wnt Signaling

Zhu, Yan; Xu, Lin; Chen, Ming; Ma, Hai-Na; Lou, Fang

doi:10.7314/apjcp.2013.14.8.4775

Cited by 18 publications

(18 citation statements)

References 24 publications

(33 reference statements)

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“…LRG4 induces, when bound by RANKL, inhibition of osteoclast differentiation which is in contrast with the effect of binding of RANKL to RANK. Although the exact relationship between LRG4 and cancer is not clear yet, it was shown that it is involved in the proliferation of several tumor cell lines [98]. Hence, future studies should also bear in mind the potential interactions between RANKL and LRG4.…”

Section: An Anti-tumor Effect Of Rankl Inhibition Mediated Via the Immentioning

confidence: 99%

The anti-tumor effect of RANKL inhibition in malignant solid tumors – A systematic review

Groot

Appelman‐Dijkstra

Burg

et al. 2018

Cancer Treatment Reviews

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At present, accumulating evidence suggests that inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) does not only induce an increase in bone mass and strength, but also has anti-tumor effects. Denosumab, an antibody targeting RANKL, is used to treat osteoporosis and to prevent skeletal related events (SREs) in patients with bone metastases originating from solid tumors. However, expression of RANKL and its receptor activator of nuclear factor kappa-B (RANK) is not solely restricted to cells involved in homeostasis of the bone and RANKL-RANK signalling appears to play a substantial role in many other processes in the body like mammary physiology, mammary tumorigenesis and the immune system. In pre-clinical models, RANKL inhibition has been shown to reduce skeletal tumor burden and distant metastases as well as to decrease mammary carcinogenesis. Clinically, RANKL inhibition improves bone-metastasis free survival in patients with prostate cancer and disease-free survival in patients with breast cancer. In addition, RANKL treatment may form a preventative strategy in patients at high risk for malignancies of the breast. Current clinical studies are evaluating the effect of denosumab on survival, the immune system and other biomarkers into a greater extent. To that purpose, a systematic review of the literature was performed and a narrative review synthesized, describing the present pre-clinical and clinical evidence of an anti-tumor effect of RANKL inhibition and the potential role of the immune system as one of the underlying mechanisms.

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Section: An Anti-tumor Effect Of Rankl Inhibition Mediated Via the Immentioning

confidence: 99%

The anti-tumor effect of RANKL inhibition in malignant solid tumors – A systematic review

Groot

Appelman‐Dijkstra

Burg

et al. 2018

Cancer Treatment Reviews

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“…[17] Transfection of ARPE-19 cells with a specific LGR4 siRNA significantly reduced LGR4 protein level after 72 hours (Fig 2A). Based on the MTS cell proliferation assay and Ki67 immunostaining results, LGR4 siRNA significantly inhibited growth of ARPE-19 cells three days after transfection (Fig 2B and 2C).…”

Section: Resultsmentioning

confidence: 99%

“…[17,20] p27 Kip1 induced LGR4 upregulation can enhance colon cancer progression and metastasis. [19] LGR4 promotes prostate tumorigenesis through PI3K/Akt signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

LGR4 Is a Direct Target of MicroRNA-34a and Modulates the Proliferation and Migration of Retinal Pigment Epithelial ARPE-19 Cells

Hou¹,

Zhou²,

Tang³

et al. 2016

PLoS ONE

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The pathology of proliferative vitreoretinopathy and proliferative diabetic retinopathy is linked to proliferation, migration, and adhesion of the retinal pigment epithelium. MicroRNA-34a (miR-34a) expression modulates changes in proliferation and migration of retinal pigment epithelial cell line ARPE-19. In this study, we determined that miR-34a interacts with LGR4, identified by bioinformatics using TargetScan Human 5.0, to affect these changes. Double luciferase gene reporter assay confirmed miR-34a involvement in mediating control. miR-34a mimic transfection decreased LGR4 expression. Western blot analysis documented corresponding protein expression inhibition. MTS, Ki67 immunostaining, scratch and transwell testing, along with attachment assay showed that miR-34a upregulation inhibited ARPE-19 cell proliferation, migration and attachment partly through downregulation of LGR4 protein expression. Western blot analysis revealed that both miR-34a upregulation and LGR4 downregulation induced declines in E2F1, p-CDC2, CDK2, CDK4 and CDK6 protein expression. Taken together, miR-34a gene expression upregulation inhibits ARPE-19 cell proliferation, migration and adhesion partly by suppressing LGR4 expression. These results substantiate earlier indications that both miR-34a and LGR4 are potential drug targets to prevent fibrosis in a clinical setting.

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“…Expression of the LGR4 receptor promotes cancer cell proliferation in multiple cell types through activation of the Wnt signaling cascade [95,96]. In cervical carcinoma cells, it correlates with enhanced cell migration and metastasis [97].…”

Section: Prognostic Value Of Lgrsmentioning

confidence: 99%

LGRs receptors as peculiar GPCRs involved in cancer

Garcia¹

2017

J Stem Cell Res Med

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G protein-coupled receptors (GPCRs) constitute the largest protein superfamily in mammalian genomes. The Leucine-rich repeat-containing G protein-coupled receptors LGR4, LGR5 and LGR6 belong to the type A rhodopsin-like family and are closely structurally related to the glycoprotein hormone receptors. They have the particularity to be expressed in stem/progenitor cells.LGRs commonly recognize R-spondins as ligands leading to Wnt signaling regulation. Whereas LGR4 plays an essential role during development and adult homeostasis and exerts a dominant function over its paralogues, the function of LGR5 still remains controversial. In cancer cells, LGRs identify tumor-initiating cells and their expression can be correlated with tumor stage and prognosis. The molecular events underlying deregulated expression of LGRs in cancer cells and potential new therapeutic approaches to target cancer cells are reviewed.

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GPR48 Promotes Multiple Cancer Cell Proliferation via Activation of Wnt Signaling

Cited by 18 publications

References 24 publications

The anti-tumor effect of RANKL inhibition in malignant solid tumors – A systematic review

The anti-tumor effect of RANKL inhibition in malignant solid tumors – A systematic review

LGR4 Is a Direct Target of MicroRNA-34a and Modulates the Proliferation and Migration of Retinal Pigment Epithelial ARPE-19 Cells

LGRs receptors as peculiar GPCRs involved in cancer

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