Wnt/β-catenin signaling in melanoma: Preclinical rationale and novel therapeutic insights

Xue, Gui-Rong; Romano, Emanuela; Massi, Daniela; Mandalà, Mario

doi:10.1016/j.ctrv.2016.06.009

Cited by 89 publications

(75 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, it seems clear that β-catenin plays a central role in other types of human cancers [7][8][9]. Recent studies have focused in other components of the pathway and their contribution to cancer development.…”

Section: Comment and Discussionmentioning

confidence: 99%

Wnt/FZD Genetics in Glioblastoma

Casas‐Tintó¹

2017

Hereditary Genet

View full text Add to dashboard Cite

Section: Comment and Discussionmentioning

confidence: 99%

Wnt/FZD Genetics in Glioblastoma

Casas‐Tintó¹

2017

Hereditary Genet

View full text Add to dashboard Cite

Section: Short Communicationmentioning

confidence: 99%

“…In the nucleus, β-catenin could form a complex with T cell factor (TCF) to regulate target gene transcriptional activation. However, in the absence of WNT, cytosolic β-catenin is phosphorylated by the complex and targeted for rapid degradation by the proteasome [5].It has been proofed that RSPO1 involves in the WNT signaling pathway; however, the potential mechanisms by which they induce β-catenin still remains unknown. More and more evidences declare that RSPO1 regulates WNT signaling by inhibiting internalization of LRP6 via antagonizing the function of DKK1.…”

mentioning

confidence: 99%

R-Spondin 1 Regulates WNT Signaling Pathway by Antagonizing the Function of Dickkopf Homolog 1

Wang¹,

Zhang²,

Zou³

2017

Single Cell Biol

View full text Add to dashboard Cite

The R-Spondin (RSPO) family of secreted proteins are implicated as potent activators of the WNT signaling pathway. R-spondins (RSPOs) consisting of four members are a group of secreted proteins which could activate the canonical WNT/β-catenin-dependent signaling pathways [1]. Dickkopf homolog 1 (DKK1) is another important player, which is a well-known inhibitor of the canonical WNT signaling pathway [2]. More and more evidences declare that RSPO1 regulates WNT signaling by antagonizing the function of DKK1.The WNT family of secreted proteins play important roles in diverse biological processes, including development, proliferation, and differentiation, which regulate various diseases, such as prostate cancer, breast cancer, glioblastoma, type II diabetes and others. The WNT ligands could activate two major intracellular pathways: known as the canonical pathway which is β-catenin-dependent, and noncanonical pathway which is β-catenin-independent [3,4].In the canonical WNT pathway, the WNT ligands could bind to their cell-surface receptors, which could lead to inactivation of Axin/ GSK3/APC complex, resulting in stabilization of cytosolic β-catenin and subsequent nuclear translocation of β-catenin. In the nucleus, β-catenin could form a complex with T cell factor (TCF) to regulate target gene transcriptional activation. However, in the absence of WNT, cytosolic β-catenin is phosphorylated by the complex and targeted for rapid degradation by the proteasome [5].It has been proofed that RSPO1 involves in the WNT signaling pathway; however, the potential mechanisms by which they induce β-catenin still remains unknown. More and more evidences declare that RSPO1 regulates WNT signaling by inhibiting internalization of LRP6 via antagonizing the function of DKK1. DKK1 has the ability to form a complex between receptors to trigger LRP5/6 internalization [2]. It has been reported by Binnerts et al. that RSPO1 could rescue the inhibition triggered by DKK1 [6]. Yin et al. demonstrated that DKK1 repressed the effect of RSPO1 on the activation of hepatic stellate cells [7], which supported that RSPO1 and DKK1 form a signaling regulation network. WNT signaling pathway was implicated in the development of breast, melanoma, prostate, lung, and other cancers, as well as Type II diabetes. It would be beneficial to declare the relationship between RSPO1, DKK1 and WNT signaling pathway.

show abstract

“…The loss or gain of function of Wnt pathway components can result in the development of hepatocellular, lung or colon cancer (13). 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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

Wnt/β-catenin signaling in melanoma: Preclinical rationale and novel therapeutic insights

Cited by 89 publications

References 103 publications

Wnt/FZD Genetics in Glioblastoma

Wnt/FZD Genetics in Glioblastoma

R-Spondin 1 Regulates WNT Signaling Pathway by Antagonizing the Function of Dickkopf Homolog 1

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

Contact Info

Product

Resources

About