The Wnt pathway and the roles for its antagonists, DKKS, in angiogenesis

Choi, Hyun Jung; Park, Hongryeol; Lee, Heon Woo; Kwon, Young Guen

doi:10.1002/iub.1062

Cited by 50 publications

(39 citation statements)

References 73 publications

(75 reference statements)

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“…Increased Dkk-1 expression in non-lesional psoriatic skin may inhibit angiogenesis by antagonising Wnt signalling thus sustaining the clinical picture of uninvolved skin. Owing to the significance of Wnt signalling in angiogenesis, Wnt antagonists, such as Dkk-1 have been considered potential treatments for neovascular disorders (17). Interestingly, DKK-1 is a pro-apoptotic gene and may play an important role in connecting the oncogenic Wnt and p53 tumour suppressor pathways (18).…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of the Wnt Signalling Inhibitor Dkk-1 in Non-lesional Skin and Peripheral Blood Mononuclear Cells of Patients with Plaque Psoriasis

Seifert¹,

Söderman²,

Skarstedt³

et al. 2015

Acta Derm Venerol

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Psoriasis is a common inflammatory skin disease characterised by abnormal keratinocyte proliferation, increased dermal angiogenesis and systemic inflammation. The cell signalling cascades provoked by Wnt proteins and their inhibitors, such as Dickkopf-1, play crucial roles to maintain homeostasis of a variety of tissues, including skin, and are also involved in angiogenesis and innate immunity. This study was designed to investigate the distribution of Dickkopf-1, in lesional and non-lesional skin, in serum and in peripheral blood mononuclear cell (PBMCs) of patients with psoriasis compared with healthy controls. Our results showed significantly increased mRNA and protein expression of Dickkopf-1 in non-lesional compared with lesional skin and healthy control skin. No significant differences of Dickkopf-1 serum levels were observed, but Dickkopf-1 protein expression was significantly increased in patients' PBMC. Increased levels of Dickkopf-1 in PBMC, suggest a possible role of Dickkopf-1 in the chronic systemic inflammation of psoriasis. Increased levels of Dickkopf-1 in non-lesional psoriasis skin offers new insights in the local inflammatory processes in psoriasis skin since Wnt signalling regulates angiogenesis. In conclusion, Dickkopf-1 may be a possible target for future treatment options.

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Section: Discussionmentioning

confidence: 99%

Increased Expression of the Wnt Signalling Inhibitor Dkk-1 in Non-lesional Skin and Peripheral Blood Mononuclear Cells of Patients with Plaque Psoriasis

Seifert¹,

Söderman²,

Skarstedt³

et al. 2015

Acta Derm Venerol

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“…Identifying alterations in the signal transduction pathways that promote lung cancer, including epigenetic modifications, may reveal biomarkers that can be used for the diagnosis and treatment of lung cancer (33). The proteins encoded by the DKK genes represent the dickkopf family of proteins, which negatively regulate the Wnt signaling pathway (12).…”

Section: Discussionmentioning

confidence: 99%

“…Certain factors of the Wnt signaling pathway have been considered as potential therapeutic targets for cancer treatment (14). Dickkopf-related proteins (DDKs) are Wnt signaling pathway inhibitors that are frequently inactivated in certain types of human cancer (12). In the present study, the expression of DKK genes in A549 cells treated by L-securinine was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).…”

Section: Introductionmentioning

confidence: 96%

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L-securinine inhibits the proliferation of A549 lung cancer cells and promotes DKK1 promoter methylation

et al. 2017

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Abstract. L-securinine is a natural product extracted and isolated from the leaf of dried Securinega suffruticosa. The aim of the present study was to explore the effects of L-securinine on proliferation, and the methylation profile of the dickkopf-related protein 1 (DKK1) gene in human lung cancer cells and fibroblasts. L-securinine was extracted, isolated and the structure was identified. The cytotoxicity of L-securinine in A549 cells was evaluated by Cell Counting Kit-8 assays. The expression and DNA methylation profile of DKK genes was analyzed by reverse transcription-quantitative polymerase chain reaction and bisulfite sequencing polymerase chain reaction, respectively. L-securinine inhibited the proliferation of lung cancer cells; the half-maximal inhibitory concentration values were 8.92, 4.73 and 3.81 µg/ml, at 24, 36 and 48 h post-treatment, respectively. DKK1, 2 and 3 expression was significantly increased in A549 cells compared with HLF-a cells. L-securinine induced the downregulation of DKK1 in A549 cells in a dose-dependent manner and induced methylation changes at CpG sites in the DKK1 promoter region. L-securinine may be a potential anticancer drug that mediates its effects by altering DKK1 gene methylation.

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“…Wnts are glycoproteins that regulate many cellular processes, including proliferation, survival, adhesion, and proliferation, by binding to the Frizzled (Fz) receptor. Wnt signaling has been shown to be important in angiogenesis and, thus, is a potential target for anti-angiogenic therapies [73]. Antagonists of Wnt signaling include secreted Frizzled-related protein (sFRP), Wnt inhibitory factor 1 (WIF-1), and Dickkopf (Dkk).…”

Section: Computational Models Of Anti-angiogenic Therapeuticsmentioning

confidence: 99%

Computational systems biology approaches to anti-angiogenic cancer therapeutics

Finley

Chu

Popel

2015

Drug Discovery Today

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Angiogenesis is an exquisitely regulated process that is required for physiological processes and is also important in numerous diseases. Tumors utilize angiogenesis to generate the vascular network needed to supply the cancer cells with nutrients and oxygen, and many cancer drugs aim to inhibit tumor angiogenesis. Anti-angiogenic therapy involves inhibiting multiple cell types, molecular targets, and intracellular signaling pathways. Computational tools are useful in guiding treatment strategies, predicting the response to treatment, and identifying new targets of interest. Here, we describe progress that has been made in applying mathematical modeling and bioinformatics approaches to study anti-angiogenic therapeutics in cancer.

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The Wnt pathway and the roles for its antagonists, DKKS, in angiogenesis

Cited by 50 publications

References 73 publications

Increased Expression of the Wnt Signalling Inhibitor Dkk-1 in Non-lesional Skin and Peripheral Blood Mononuclear Cells of Patients with Plaque Psoriasis

Increased Expression of the Wnt Signalling Inhibitor Dkk-1 in Non-lesional Skin and Peripheral Blood Mononuclear Cells of Patients with Plaque Psoriasis

L-securinine inhibits the proliferation of A549 lung cancer cells and promotes DKK1 promoter methylation

Computational systems biology approaches to anti-angiogenic cancer therapeutics

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