Dickkopfs and Wnt/β-catenin signalling in liver cancer

Fatima, Sarwat

doi:10.5306/wjco.v2.i8.311

Cited by 53 publications

(44 citation statements)

References 161 publications

(193 reference statements)

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“…The Wnt pathway drives proliferation, maintains survival and promotes stemness in cancer cells (Klaus and Birchmeier 2008), and plays a well-known role in HCC tumorigenesis ( Whittaker et al 2010;Fatima et al 2011). Overall, 62.5% of tumors in the cohort contain genomic alterations composed of SNV and CNV affecting core components of the Wnt pathway (Fig.…”

Section: Frequently Altered Cancer Pathwaysmentioning

confidence: 99%

Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma

et al. 2013

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Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment, yet the molecular basis of hepatocarcinogenesis remains largely unknown. Here we report findings from a whole-genome sequencing (WGS) study of 88 matched HCC tumor/normal pairs, 81 of which are Hepatitis B virus (HBV) positive, seeking to identify genetically altered genes and pathways implicated in HBV-associated HCC. We find beta-catenin to be the most frequently mutated oncogene (15.9%) and TP53 the most frequently mutated tumor suppressor (35.2%). The Wnt/beta-catenin and JAK/STAT pathways, altered in 62.5% and 45.5% of cases, respectively, are likely to act as two major oncogenic drivers in HCC. This study also identifies several prevalent and potentially actionable mutations, including activating mutations of Janus kinase 1 (JAK1), in 9.1% of patients and provides a path toward therapeutic intervention of the disease.

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Section: Frequently Altered Cancer Pathwaysmentioning

confidence: 99%

Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma

et al. 2013

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“…Wnt/β-catenin signaling has emerged as a critical player in both the development of normal liver as well as an oncogenic driver in hepatocellular carcinoma (HCC) [19, 20]. It has been reported that 40%-70% of HCC patients have tumors with high levels of β-catenin accumulation [21-24].…”

Section: Fzd7 In Cancermentioning

confidence: 99%

“…Mutations in the β-catenin gene were found in 12-26% of HCCs, while mutations in APC and Axin2 are very rare [25]. Recent studies indicate that dysregulation of Wnt/β-catenin signaling in HCC is also due to the aberrant epigenetic regulation of several Wnt signaling antagonists [26-30] and/or the up-regulation of cell surface Wnt proteins and their receptors [20]. The Fzd7 steady-state mRNA levels are up-regulated in hepatitis B, C, and nonviral-induced HCC cell lines and mouse models [27, 31, 32].…”

Section: Fzd7 In Cancermentioning

confidence: 99%

Frizzled7 as an emerging target for cancer therapy

King

Zhang

Suto

et al. 2012

Cellular Signalling

109

112

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Wnt proteins are secreted glycoproteins that bind to the N-terminal extra-cellular cysteine-rich domain of the Frizzled (Fzd) receptor family. The Fzd receptors can respond to Wnt proteins in the presence of Wnt co-receptors to activate the canonical and non-canonical Wnt pathways. Recent studies indicated that, among the Fzd family, Fzd7 is the Wnt receptor most commonly upregulated in a variety of cancers including colorectal cancer, hepatocellular carcinoma and triple negative breast cancer. Fzd7 plays an important role in stem cell biology and cancer development and progression. In addition, it has been demonstrated that siRNA knockdown of Fzd7, the anti-Fzd7 antibody or the extracellular peptide of Fzd7 (soluble Fzd7 peptide) displayed anti-cancer activity in vitro and in vivo mainly due to the inhibition of the canonical Wnt signaling pathway. Furthermore, pharmacological inhibition of Fzd7 by small interfering peptides or a small molecule inhibitor suppressed β-catenin-dependent tumor cell growth. Therefore, targeted inhibition of Fzd7 represents a rational and promising new approach for cancer therapy.

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“…One such relevant pathway is the Wnt/ β -catenin signaling cascade which plays a decisive role in cell fate, favoring cell proliferation over apoptosis. Accumulating evidence has shown that the canonical Wnt/ β -catenin pathway is frequently activated in HCC and responsible for initiation and progression of the disease [13–16], and this pathway could be an attractive and viable target for chemoprevention and therapy of HCC [17–19]. …”

Section: Introductionmentioning

confidence: 99%

Pomegranate Bioactive Constituents Suppress Cell Proliferation and Induce Apoptosis in an Experimental Model of Hepatocellular Carcinoma: Role of Wnt/β-Catenin Signaling Pathway

Bhatia

Thoppil

Mandal

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, and chemoprevention represents a viable approach in lowering the mortality of this disease. Pomegranate fruit, an abundant source of anti-inflammatory phytochemicals, is gaining tremendous attention for its wide-spectrum health benefits. We previously reported that a characterized pomegranate emulsion (PE) prevents diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis though inhibition of nuclear factor-kappaB (NF-κB). Since NF-κB concurrently induces Wnt/β-catenin signaling implicated in cell proliferation, cell survival, and apoptosis evasion, we examined antiproliferative, apoptosis-inducing and Wnt/β-catenin signaling-modulatory mechanisms of PE during DENA rat hepatocarcinogenesis. PE (1 or 10 g/kg) was administered 4 weeks before and 18 weeks following DENA exposure. There was a significant increase in hepatic proliferation (proliferating cell nuclear antigen) and alteration in cell cycle progression (cyclin D1) due to DENA treatment, and PE dose dependently reversed these effects. PE substantially induced apoptosis by upregulating proapoptotic protein Bax and downregulating antiapoptotic protein Bcl-2. PE dose dependently reduced hepatic β-catenin and augmented glycogen synthase kinase-3β expression. Our study provides evidence that pomegranate phytochemicals exert chemoprevention of hepatic cancer through antiproliferative and proapoptotic mechanisms by modulating Wnt/β-catenin signaling. PE, thus, targets two interconnected molecular circuits (canonical NF-κB and Wnt/β-catenin pathways) to exert chemoprevention of HCC.

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Dickkopfs and Wnt/β-catenin signalling in liver cancer

Cited by 53 publications

References 161 publications

Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma

Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma

Frizzled7 as an emerging target for cancer therapy

Pomegranate Bioactive Constituents Suppress Cell Proliferation and Induce Apoptosis in an Experimental Model of Hepatocellular Carcinoma: Role of Wnt/β-Catenin Signaling Pathway

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