Non-canonical WNT6/WNT10A signal factor expression in EBV+ post-transplant smooth muscle tumors

Teiken, Kristin; Rehkaemper, Jan; Kreipe, Hans; Laenger, Florian; Hussein, Kais; Jonigk, Danny

doi:10.1186/s13569-018-0096-8

Cited by 8 publications

(3 citation statements)

References 30 publications

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“…Interestingly, WNT6 and WNT10A are located immediately adjacent to one another on chromosome 2 suggesting co-regulation of respective promotors (30), and co-expression has also been shown in the placenta (31). While typically related to canonical Wnt activation, their co-expression has also been linked to non-canonical Wnt signaling (32). FZD2 and FZD4 expression are restricted to villous mesenchymal cells, which are important in triggering trophoblast invasion (33).…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of the secreted wingless agonist R-spondin 3 in preeclamptic pregnancies

Ueland

Estensen

Grindheim³

et al. 2020

Journal of Hypertension

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Objective: Preeclampsia is a syndrome characterized by hypertension and poor placental development. The developmental Wnt pathway plays an important role in placental development and we hypothesized that Wnt signaling would be dysregulated in preeclampsia.Methods: To elucidate aberrations in the Wnt signaling pathway we conducted a pathway analysis on placental mRNA in late-onset preeclampsia and normal pregnancy from the STORK study (n=10 in each group, RNAseq) to identify differentially expressed genes. In addition, we compared circulating levels of secreted Wnt agonists and antagonists at term pregnancy and 6 months post-partum from an acute preeclampsia study (preeclampsia n=34, normal pregnancy n=61).Results: We found circulating and placental mRNA levels of the secreted Wnt agonist RSPO3 at term elevated in preeclampsia. Increased plasma RSPO3 was associated with high mean arterial pressure. Further, pathway analysis of placental tissue revealed elevated mRNA levels of upstream ligands WNT6 and WNT10A and frizzled receptors 2 and 4 in preeclampsia and downstream activation of the non-canonical Ca 2+ /NFAT pathway. Finally, plasma DKK3 was decreased in preeclampsia 6 months post-partum. Conclusion:We identify a potential role for RSPO3 and activation of non-canonical Wnt signaling in preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Elevated levels of the secreted wingless agonist R-spondin 3 in preeclamptic pregnancies

Ueland

Estensen

Grindheim³

et al. 2020

Journal of Hypertension

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“…It is noteworthy to mention that aberrant activation of Wnt signaling pathways is obviously not limited to the four cancer types mentioned below. Various Wnt ligands, the agonist Norrin, Fz receptors and the co-receptors Lrp6 and Ror1/2 have been reported to be abnormally expressed and associated with metastatic behavior, cancer progression and chemoresistance in ovarian cancer, glioblastoma multiforme, chronic lymphocytic leukemia, melanoma, multiple myeloma, post-transplant smooth muscle tumor, prostate cancer, pancreatic cancer gastric cancer, oral squamous cell carcinoma, Ewing sarcoma, osteosarcoma, and malignant peripheral nerve sheath tumors ( Derksen et al, 2004 ; Larue and Delmas, 2006 ; Dissanayake et al, 2007 ; Yan et al, 2016 ; Yu et al, 2016 ; Li et al, 2017 , 2019a ; Liu et al, 2017 ; Pridgeon et al, 2017 ; Sandsmark et al, 2017 ; Jiang et al, 2018 ; Sinnberg et al, 2018 ; Teiken et al, 2018 ; Yang et al, 2019b ; Chehover et al, 2020 ; El-Sehemy et al, 2020 ; Frenquelli et al, 2020 ; Kotrbova et al, 2020 ). Thus, a thorough understanding of misregulation of Wnt signaling pathways at the plasma membrane will pave the way for new therapeutic approaches for cancer.…”

Section: Misregulation Of Wnt Signaling Pathways At the Plasma Membramentioning

confidence: 99%

Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer

Azbazdar

Karabicici

Erdal

et al. 2021

Front. Cell Dev. Biol.

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Wnt signaling is one of the key signaling pathways that govern numerous physiological activities such as growth, differentiation and migration during development and homeostasis. As pathway misregulation has been extensively linked to pathological processes including malignant tumors, a thorough understanding of pathway regulation is essential for development of effective therapeutic approaches. A prominent feature of cancer cells is that they significantly differ from healthy cells with respect to their plasma membrane composition and lipid organization. Here, we review the key role of membrane composition and lipid order in activation of Wnt signaling pathway by tightly regulating formation and interactions of the Wnt-receptor complex. We also discuss in detail how plasma membrane components, in particular the ligands, (co)receptors and extracellular or membrane-bound modulators, of Wnt pathways are affected in lung, colorectal, liver and breast cancers that have been associated with abnormal activation of Wnt signaling. Wnt-receptor complex components and their modulators are frequently misexpressed in these cancers and this appears to correlate with metastasis and cancer progression. Thus, composition and organization of the plasma membrane can be exploited to develop new anticancer drugs that are targeted in a highly specific manner to the Wnt-receptor complex, rendering a more effective therapeutic outcome possible.

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“…Wnt6, a member of the Wnt protein family, is always coexpressed with Wnt10a. These molecules are both highly expressed in carcinogenesis and cell proliferation [53]. Nevertheless, how Wnt6 is activated and further inhibits EZH2 after NOX4 overexpression remains unclear.…”

Section: Figmentioning

confidence: 99%

A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration

Liu

Yang

et al. 2020

Cell Div

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Background: The senescence of nucleus pulposus (NP) cells plays a vital role in the pathogenesis of intervertebral disc (IVD) degeneration (IDD). NADPH oxidase 4 (NOX4)-associated oxidative stress has been shown to induce premature NP cell senescence. Enhancer of zeste homolog 2 (EZH2) is a crucial gene regulating cell senescence. The aim of this study was to investigate the roles of EZH2 in NOX4-induced NP cell senescence and a feedback loop between EZH2 and NOX4. Results: The down-regulation of EZH2 and the up-regulation of NOX4 and p16 were observed in the degenerative discs of aging rats. EZH2 regulated NP cell senescence via the H3K27me3-p16 pathway. Also, EZH2 regulated the expression of NOX4 in NP cells through the histone H3 lysine 27 trimethylation (H3K27me3) in the promoter of NOX4 gene. Furthermore, NOX4 down-regulated EZH2 expression in NP cells via the canonical Wnt/β-catenin pathway. Conclusions: A positive feedback loop between EZH2 and NOX4 is involved in regulating NP cell senescence, which provides a novel insight into the mechanism of IDD and a potential therapeutic target for IDD.

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Non-canonical WNT6/WNT10A signal factor expression in EBV+ post-transplant smooth muscle tumors

Cited by 8 publications

References 30 publications

Elevated levels of the secreted wingless agonist R-spondin 3 in preeclamptic pregnancies

Elevated levels of the secreted wingless agonist R-spondin 3 in preeclamptic pregnancies

Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer

A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration

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