WNT signaling in malignant mesothelioma

10.2741/1953 ◽  
2006 ◽  
Vol 11 (1) ◽  
pp. 2106 ◽  
Author(s):  
Simon Fox
Keyword(s):  
Wnt Signaling ◽  
Malignant Mesothelioma

A Succinate Ether Derivative of Tocotrienol Enhances Dickkopf-1 Gene Expression through Epigenetic Alterations in Malignant Mesothelioma Cells

Pharmacology ◽  
2018 ◽  
Vol 102 (1-2) ◽  
pp. 26-36 ◽  
Author(s):  
Ayami Sato ◽  
Haruka Ueno ◽  
Momoka Fusegi ◽  
Saki Kaneko ◽  
Kakeru Kohno ◽  
...  
Keyword(s):  
Cell Viability ◽  
Wnt Signaling ◽  
Malignant Mesothelioma ◽  
Methylation Status ◽  
Dna Methyltransferases ◽  
Tumor Growth Inhibition ◽  
Cytotoxic Effects ◽  
Ether Derivative ◽  
Dkk1 Expression ◽  
Dickkopf 1

Background: Wnt signaling plays an essential role in tumor cell growth, including the development of malignant mesothelioma (MM). Epigenetic silencing of negative Wnt regulators leading to constitutive Wnt signaling has been observed in various cancers and warrants further attention. We have reported that a succinate ether derivative of α-tocotrienol (T3E) has potent cytotoxic effects in MM cells. Thus, in this study, we investigated whether the anti-MM effect of T3E could be mediated via the epigenetic alteration of the Wnt antagonist gene, Dickkopf-1 (DKK1). Methods: WST-1 and cell analyzers were employed to analyze the effects of T3E on cell viability and apoptosis of human MM cell lines (H2452, H28). Real-time PCR and Western blot were performed to evaluate the expression at mRNA and protein levels. Methylation status and epigenetic modifications of DKK1’s promoter regions after T3E treatment in MM cells were studied using methylation-specific PCR and Chromatin immunoprecipitation. Small interfering RNA-mediated knockdown ­(siRNA), and specific inhibitors, were used to validate DKK1 as a target of T3E. Results: T3E markedly impaired MM cell viability, increased the expression of phosphorylated-JNK and DKK1 and suppressed cyclin D, a downstream target gene of Wnt signaling. Knockdown of DKK1 expression by siRNA or a specific JNK inhibitor confirmed the contribution of DKK1 and JNK to T3E-induced cytotoxicity in MM cells. On the other hand, cytoskeleton-associated protein 4 (CKAP4) expression, which promotes cell proliferation as a Wnt-independent DKK1 receptor was inhibited by T3E. Silencing CKAP4 by ­siRNA did not appear to directly affect MM cell viability, thereby indicating that expression of both DKK1 and CKAP4 is required. Furthermore, T3E-mediated inhibition of both DNA methyltransferases (DNMT1, 3A, and 3B) and histone deacetylases (HDAC1, 2, 3, and 8) in MM cells leads to increased DKK1 expression, thereby promoting tumor growth inhibition. MM cells treated with Zebularine (a DNMT inhibitor) and sodium butyrate (an HDAC inhibitor) exhibited cytotoxic effects, which may explain the inhibitory action of T3E on MM cells. In addition, an enhanced expression of DKK1 in MM cells following T3E treatment is positively correlated with the methylation status of its promoter; T3E decreased DNA methylation and increased histone acetylation. Moreover, T3E specifically increased histone H3 lysine 4 (H3K4) methylation activity, whereas no effects were observed on histone H3K9 and H3K27. Conclusions: Targeting the epigenetic induction of DKK1 may lead to effective treatment of MM, and T3E has great potential to induce anti-MM activity.

Expression profile and function of Wnt signaling mechanisms in malignant mesothelioma cells

2013 ◽  
Vol 440 (1) ◽  
pp. 82-87 ◽  
Author(s):  
Simon A. Fox ◽  
Alex K. Richards ◽  
Ivonne Kusumah ◽  
Vanathi Perumal ◽  
Erin M. Bolitho ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Malignant Mesothelioma ◽  
Expression Profile ◽  
Signaling Mechanisms ◽  
And Function

Ultrastructural diagnosis of peritoneal malignant mesothelioma

1994 ◽  
Vol 52 ◽  
pp. 234-235
Author(s):  
S. Siew
Keyword(s):  
Malignant Mesothelioma ◽  
Common Type ◽  
Abdominal Discomfort ◽  
The Body ◽  
Metastatic Adenocarcinoma ◽  
Common Site ◽  
Primary Malignancy ◽  
Peritoneal Implant ◽  
Morphological Diagnosis ◽  
Malignant Neoplasia

Mesothelial cells constitute the lining of the three serous sacs of the body i.e. the pleura, pericardium and peritoneum. The more common type of malignant neoplasia of the serous sacs is seeding by metastatic tumors and primary malignancy of the mesothelium is unusual. Of the three sacs, the pleura is the most common site of malignant mesothelioma. Involvement of the peritoneum is extremely rare.We report 3 cases of malignant mesothelioma of the peritoneum. All of them were female. Their ages were 57, 67 and 72 years, respectively. The patients presented with abdominal discomfort and/or ascites. The extent of the tumors ranged from a peritoneal implant to widespread infiltration of the peritoneum and omentum. Histologic examination in Case 1 showed the presence of a diffusely infiltrating papillary mesothelioma without a sarcomatoid component. A mesodermal element was present in the other two cases. In order to establish a morphological diagnosis of malignant mesothelioma, the possibility has to be excluded of a metastatic adenocarcinoma.

Wnt signaling pathway regulates the differentiation of hepatic progenitor cells

2010 ◽  
Vol 34 (8) ◽  
pp. S41-S41
Author(s):  
Yang Bi ◽  
Yun He ◽  
Tingyu Li ◽  
Tao Feng ◽  
Tongchuan He
Keyword(s):  
Wnt Signaling ◽  
Progenitor Cells ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Hepatic Progenitor Cells

417: The Human Androgen Receptor Gene is a Primary Target of the WNT Signaling Pathway

2006 ◽  
Vol 175 (4S) ◽  
pp. 136-136
Author(s):  
Ralph Buttyan ◽  
Xuezhen Yang ◽  
Min-Wei Chen ◽  
Debra L. Bemis ◽  
Mitchell C. Benson ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Receptor Gene ◽  
Wnt Signaling Pathway ◽  
Androgen Receptor Gene ◽  
Primary Target ◽  
Human Androgen Receptor Gene ◽  
Human Androgen Receptor

Wnt Signaling Pathway in Right Ventricular Remodeling

Pneumologie ◽  
2012 ◽  
Vol 66 (06) ◽  
Author(s):  
A Tretyn ◽  
KD Schlüter ◽  
W Janssen ◽  
HA Ghofrani ◽  
F Grimminger ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Ventricular Remodeling ◽  
Wnt Signaling Pathway ◽  
Right Ventricular Remodeling

microRNA and WNT signaling

2016 ◽  
Author(s):  
Eric Hesse
Keyword(s):  
Wnt Signaling
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