The Role of Wnt/Beta-Catenin Signaling in Renal Carcinogenesis: Lessons from Cadmium Toxicity Studies

Thévenod, Frank; Chakraborty, Prabir K.

doi:10.2174/156652410791316986

Cited by 48 publications

(35 citation statements)

References 240 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When the Wnt/β-catenin signaling pathway is activated, β-catenin protein competitively binds TCF after entering the nucleus; thereby the transcription of target genes is enhanced (Thevenod et al, 2010). In the present study, TCF4 protein expression was increased with the aggravation of gastric mucosal lesions, and the positive rate of the expression in intestinal type GC was higher than that in diffuse GC.…”

Section: 215 Wnt Pathway Expression and Hpylori Infection In Gastrisupporting

confidence: 45%

“…TCF4 is the downstream protein of the Wnt/β-catenin signaling pathway and plays the role of a molecular switch in the pathway (Thevenod et al, 2010). When the Wnt/β-catenin signaling pathway is activated, β-catenin protein competitively binds TCF after entering the nucleus; thereby the transcription of target genes is enhanced (Thevenod et al, 2010).…”

Section: 215 Wnt Pathway Expression and Hpylori Infection In Gastrimentioning

confidence: 99%

See 1 more Smart Citation

Expression of the E-cadherin/β-catenin/tcf-4 Pathway in Gastric Diseases with Relation to Helicobacter pylori Infection: Clinical and Pathological Implications

Yu¹,

Xu²,

Xu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Objective: To determine the expression of E-cadherin, β-catenin, and transcription factor 4 (TCF4) proteins in gastric diseases with relation to Helicobacter pylori infection. Methods: A total of 309 patients including 60 with superficial gastritis (SG), 57 with atrophic gastritis (AG) and 192 with gastric cancer (GC), were enrolled. The expression of E-cadherin, β-catenin, TCF4 proteins in the gastric mucosa was detected by immunohistochemistry and H. pylori infection by immunohistochemistry and PCR. Results: The expression rates of E-cadherin were significantly higher in SG and AG than in GC (P<0.01), while those of β-catenin in the nucleus were significantly lower in SG and AG than in GC (P<0.05). In GC cases, the expression rates of E-cadherin, β-catenin and TCF4 were significantly higher in the intestinal type than in the diffuse type (P<0.05). In GC patients, the expression rate of E-cadherin was significantly higher in the presence of H. pylori than in the absence of infection (P=0.011). Moreover, the expression level of TCF4 and β-catenin protein was significantly higher in the nucleus and cytoplasm in H. pylori positive than in H. pylori negative GC patients, especially in those with the intestinal type (all P < 0.05). Conclusion: The expression of E-cadherin and β-catenin progressively decreases during the process of GC tumorigenesis, while overexpression of TCF4 occurs. H. pylori infection is associated with a significant increase in the expression of E-cadherin and β-catenin in the cytoplasm and nucleus in GC patients, especially those with the intestinal type.

show abstract

Section: 215 Wnt Pathway Expression and Hpylori Infection In Gastrisupporting

confidence: 45%

Section: 215 Wnt Pathway Expression and Hpylori Infection In Gastrimentioning

confidence: 99%

Expression of the E-cadherin/β-catenin/tcf-4 Pathway in Gastric Diseases with Relation to Helicobacter pylori Infection: Clinical and Pathological Implications

Yu¹,

Xu²,

Xu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…Under normal conditions, b-catenin enhances cell proliferation and differentiation through Wnt signaling (Daugherty and Gottardi, 2007;Hoogeboom and Burgering, 2009;Thévenod and Chakraborty, 2010). It also serves as a mediator that promotes cell survival under conditions of ROS challenge, which would increase stress resistance and ROS clearance.…”

mentioning

confidence: 99%

“…It also serves as a mediator that promotes cell survival under conditions of ROS challenge, which would increase stress resistance and ROS clearance. b-Catenin interacts with some transcription factors activated by ROS challenge, such as HIF-1, c-Jun, TCF and Foxo (Thévenod and Chakraborty, 2010). Interactions of b-catenin with these molecules enhance the transcriptional activity of target genes (Thévenod and Chakraborty, 2010).…”

mentioning

confidence: 99%

E-cadherin inhibits nuclear accumulation of Nrf2: implications for chemoresistance of cancer cells

Kim

Cho

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

SummaryNrf2 has an anti-carcinogenic effect. However, an increase in Nrf2 activity is also implicated in cancer chemoresistance. A switch from E-cadherin to N-cadherin affects the transdifferentiation and metastasis of cancer cells. In view of the key role of this switch in cancer malignancy, we investigated the regulatory effect of E-cadherin on Nrf2. In HEK293 cells, overexpression of E-cadherin inhibited the nuclear accumulation of Nrf2, and prevented Nrf2-dependent gene induction. GST pull-down and immunocytochemical assays verified the interaction between E-cadherin and Nrf2: E-cadherin bound the C-terminus of Nrf2, but not its N-terminus, which comprises the Neh2 domain responsible for phosphorylation of Ser40. Our finding that the mutation of Ser40 to alanine in Nrf2 did not affect the ability of E-cadherin to bind Nrf2 and repress target gene transactivation suggests that E-cadherin might not disturb the phosphorylation. Studies using mutant constructs of E-cadherin suggested that the b-catenin-binding domain contributes to the inhibitory effect of Ecadherin on Nrf2. Consistently, knockdown of b-catenin attenuated not only the effect of E-cadherin binding to Nrf2, but also Keap1-dependent ubiquitylation of Nrf2, and thereby increased Nrf2 activity, supporting the involvement of b-catenin in the interactions. Collectively, E-cadherin recruits Nrf2 through b-catenin, and assists the function of Keap1 for the inhibition of nuclear localization and transcriptional activity of Nrf2. In HepG2 cells, the loss of E-cadherin by either siRNA knockdown or treatment with TGFb1 enhanced the constitutive or inducible activity of Nrf2, implying that chemoresistance of cancer cells upon the loss of E-cadherin might be associated with Nrf2.

show abstract

“…β-catenin-mediated signaling regulates a diverse set of genes responsible for cell proliferation, differentiation and homeostasis (26)(27)(28). To scrutinize which downstream factor accounts for the cell apoptosis induced by Baohuoside-I, we examined the expression levels of the factors, including survivin and cyclin D1.…”

Section: Baohuoside-i Inhibits β-Catenin Activity and Decreases The Ementioning

confidence: 99%

The flavonoid Baohuoside-I inhibits cell growth and downregulates survivin and cyclin D1 expression in esophageal carcinoma via β-catenin-dependent signaling

Wang

An²,

Liu³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

Abstract. Esophageal cancer is one of the most common malignancies and is associated with a dismal prognosis. Although treatment options have increased for some patients, overall progress has been modest. Thus, there is a great need to develop new treatments. We found that Baohuoside-I, a flavonoid extracted from a Chinese medicinal plant, exhibits anticancer activity. Here, we demonstrated that Baohuoside-I significantly inhibited Eca109 human esophageal squamous carcinoma cell proliferation and induced Eca109 cell apoptosis in vitro and in vivo. The growth inhibitory effect of Baohuoside-I on the Eca109 tumor cell line was examined by MTT assay; the induction of apoptosis was analyzed by flow cytometry. Eca109-luc cells were injected into the subcutaneous tissue of nude mice to establish xenograft tumors. Our results revealed that Baohuoside-I caused a dose-and timedependent inhibition of cell growth and an induction of apoptosis. Furthermore, Baohuoside-I-treated cells were characterized by decreased expression of the β-catenin gene and protein in the total cell lysates. Thus, the gene and protein expression of the downstream elements survivin and cyclin D1 was downregulated. To determine the precise inhibitory mechanisms involved, further in-depth in vivo studies of Baohuoside-I are warranted. Our study provides the first evidence that Baohuoside-I inhibits tumor growth and induces apoptosis by inhibiting β-catenin-dependent signaling pathways. Thus, Baohuoside-I is a potential candidate in ESCC disease therapy. IntroductionEsophageal cancer is one of the most common cancers and one of the main causes of cancer-related death in the world (1,2). Cancer of the esophagus is associated with a very poor survival rate. Even in the most developed countries, the 5-year survival rate ranges merely from 10 to 16% (3). In China, the mortality rate of esophageal cancer is ranked fourth among all cancer-related deaths, and esophageal squamous cell carcinoma (ESCC) is the major histological type (4,5). Despite significant advances in screening, surgical care and chemoradiotherapy techniques, the prognosis for patients with ESCC remains poor (6,7). Thus, it is necessary to search for new treatment strategies.Herbal and natural products are valuable resources for anticancer drugs (8). Plant-derived active constituents and their semi-synthetic and synthetic analogs have served as one of the major sources for new anticancer drugs (9,10). Several plantderived anticancer agents, such as flavopiridol, acronycine, bruceantin and thalicarpine, are currently being used in clinical trials in the US (10). Thus, natural products have been the mainstay of cancer chemotherapy for the past few decades (10).Recently, by screening hundreds of traditional Chinese medicines, we found that extracts of Cortex periplocae (CP) possess cancer-preventative properties. CP is the dry root of the traditional Chinese herb Periploca sepium Bunge, referred to as Xiangjiapi in Chinese. It is a traditional type of medicine commonly used for a variety of c...

show abstract

The Role of Wnt/Beta-Catenin Signaling in Renal Carcinogenesis: Lessons from Cadmium Toxicity Studies

Cited by 48 publications

References 240 publications

Expression of the E-cadherin/β-catenin/tcf-4 Pathway in Gastric Diseases with Relation to Helicobacter pylori Infection: Clinical and Pathological Implications

Expression of the E-cadherin/β-catenin/tcf-4 Pathway in Gastric Diseases with Relation to Helicobacter pylori Infection: Clinical and Pathological Implications

E-cadherin inhibits nuclear accumulation of Nrf2: implications for chemoresistance of cancer cells

The flavonoid Baohuoside-I inhibits cell growth and downregulates survivin and cyclin D1 expression in esophageal carcinoma via β-catenin-dependent signaling

Contact Info

Product

Resources

About