The β-catenin/TCF complex as a novel target of resveratrol in the Wnt/β-catenin signaling pathway

Chen, Hui-Jye; Hsu, Le-Shiang; Shia, Yu-Ting; Lin, Ming-Tzer; Lin, Chung-Ming

doi:10.1016/j.bcp.2012.08.011

Cited by 98 publications

(77 citation statements)

References 45 publications

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“…This study found resveratrol not only disrupted Wnt signaling, but also abrogated Notch and STAT3 signaling. Although resveratrol inhibits the Wnt pathway, possibly by disrupting the β-catenin/TCF interaction (Figure 1 [Chen et al, 2012]), its mechanism may not be specific to cancer cells. When ingested by patients, resveratrol appeared to primarily target the normal colon mucosa (Nguyen et al, 2009a).…”

Section: Targeting the Wnt Pathwaymentioning

confidence: 99%

Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28

McDermott

Jimeno

2015

Pharmacology & Therapeutics

203

167

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The Wnt signaling pathways are a group of signal transduction pathways that play an important role in cell fate specification, cell proliferation and cell migration. Aberrant signaling in these pathways has been implicated in the development and progression of multiple cancers by allowing increased proliferation, angiogenesis, survival and metastasis. Activation of the Wnt pathway also contributes to the tumorigenicity of cancer stem cells (CSCs). Therefore, inhibiting this pathway has been a recent focus for cancer research with multiple targetable candidates in development. OMP-54F28 is a fusion protein that combines the cysteine-rich domain of frizzled family receptor 8 (Fzd8) with the immunoglobulin Fc domain that competes with the native Fzd8 receptor for its ligands and antagonizes Wnt signaling. Preclinical models with OMP-54F28 have shown reduced tumor growth and decreased CSC frequency as a single agent and in combination with other chemotherapeutic agents. Due to these findings, a phase 1a study is nearing completion with OMP-54F28 in advanced solid tumors and 3 phase 1b studies have been opened with OMP-54F28 in combination with standard of care chemotherapy backbones in ovarian, pancreatic and hepatocellular cancers. This article will review the Wnt signaling pathway, preclinical data on OMP-54F28 and other Wnt pathway inhibitors and ongoing clinical trials.

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Section: Targeting the Wnt Pathwaymentioning

confidence: 99%

Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28

McDermott

Jimeno

2015

Pharmacology & Therapeutics

203

167

View full text Add to dashboard Cite

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“…20 The b-catenin/T-cell factor (TCF) complex may be a target of resveratrol in the Wnt/b-catenin signalling pathway. 21 In a recent study, Ozdemir et al 22 reported that resveratrol attenuated hyperoxia-induced lung injury in newborn rats, but the underlying mechanism has not been investigated and the results were incomplete. Based on the evidence described above, there is reason to hypothesize that resveratrol alleviates lung injury in hyperoxia-exposed neonatal rats via its antioxidative, anti-inflammatory and Wnt/b-catenin signalling pathway regulating effects.…”

Section: Introductionmentioning

confidence: 97%

Resveratrol attenuates hyperoxia‐induced oxidative stress, inflammation and fibrosis and suppresses Wnt/β‐catenin signalling in lungs of neonatal rats

Zhao

Zhang

et al. 2015

Clin Exp Pharma Physio

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Although survival rate of infants born prematurely has been raised by supplemental oxygen treatment, it is followed by high morbidity of hyperoxia-induced bronchopulmonary dysplasia. In this study, the effect of resveratrol on the lung injury was evaluated in hyperoxia-exposed rats of preterm birth. The results demonstrated that hyperoxia led to thickened alveolar wall, simplified alveolar architecture and fibrosis. In addition, elevated methane dicarboxylic aldehyde level, decreased glutathione level and superoxide dismutase activity were also found in hyperoxic lungs, as well as the increased tumor necrosis factor-α, interleukin-1β and interleukin-6 in the bronchoalveolar lavage fluid. Fibrotic-associated proteins transforming growth factor-β1, α-smooth muscle actin, collagen I and fibronectin deposition were also found in interstitial substance of lungs. Furthermore, Wnt/β-catenin signalling was found to be active in hyperoxia-induced lungs. In addition, expression of SP-C was increased and T1α was decreased in hyperoxia-exposed lungs. Resveratrol intraperitoneal administration alleviated hyperoxia-induced histological injury of lungs, regulated redox balance, decreased pro-inflammatory cytokine release, and down-regulated expression of fibrotic-associated proteins. Furthermore, Wnt/β-catenin signalling was also suppressed by resveratrol, as represented by diminished expression of lymphoid enhancer factor-1, Wnt induced signalling protein-1 and cyclin D1. In addition, the increase of SP-C and decrease of T1α expression was prevented as well. The present study showed that resveratrol could protect lungs from hyperoxia-induced injury through its antioxidant, anti-inflammatory and anti-fibrotic effects. The transdifferentiation of alveolar epithelial type II cells to alveolar epithelial type I cells promotion and Wnt/β-catenin signalling suppression are also involved in the protective effect.

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“…The Wnt/β-catenin pathway involved in the early development process of various types of cancer is also involved in the development of CRC (6,7). The key step in activating the Wnt pathway is the stabilization of β-catenin and its translocation into the nucleus, which may serve as a potential target for CRC therapy (8).…”

Section: Introductionmentioning

confidence: 99%

Silencing of pancreatic adenocarcinoma upregulated factor by RNA interference inhibits the malignant phenotypes of human colorectal cancer cells

Liu

et al. 2013

Oncology Reports

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Abstract. Aberrant expression of pancreatic adenocarcinoma upregulated factor (PAUF), a novel secretory protein, has been reported in several types of cancer. However, in colorectal cancer (CRC), whether PAUF also plays its oncogenic role through the Wnt/β-catenin pathway and its effect in regulating malignant phenotypes of CRC is unknown. In this study, we detected PAUF and β-catenin expression levels by immunohistochemical analysis and real-time PCR in CRC tissues, adjacent non-tumor tissues (NATs) and 5 CRC cell lines. The results demonstrated that the expression of PAUF and β-catenin in tumor tissues was higher than in NATs. Moreover, the expression of PAUF was correlated with the expression of β-catenin in both tumor tissues and NATs. The HCT116 cell line, which has the highest PAUF expression of the 5 cell lines, was transfected with small interfering RNA (siRNA) targeting on PAUF, which significantly downregulated the expression of PAUF in cancer cells. Successful transfection was confirmed by using RT-PCR and western blot analysis. Further studies demonstrated that PAUF-siRNA inhibited the proliferation of CRC cells, promoted their apoptosis and induced G0/G1 cell cycle arrest. At the same time, PAUF-siRNA inhibited the invasion, adhesion and migration of the tumor cells. In conclusion, this study suggested that PAUF was expressed in CRC at a high frequency. Interference of PAUF may be an effective strategy for regulating malignant phenotypes of CRC through the Wnt/β-catenin pathway.

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The β-catenin/TCF complex as a novel target of resveratrol in the Wnt/β-catenin signaling pathway

Cited by 98 publications

References 45 publications

Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28

Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28

Resveratrol attenuates hyperoxia‐induced oxidative stress, inflammation and fibrosis and suppresses Wnt/β‐catenin signalling in lungs of neonatal rats

Silencing of pancreatic adenocarcinoma upregulated factor by RNA interference inhibits the malignant phenotypes of human colorectal cancer cells

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