Genetic alterations of Wnt signaling pathway–associated genes in hepatocellular carcinoma

Kim, Young-Dae; Park, Chang-Hwan; Kim, Hyunsoo; Choi, Sungkyu; Rew, Jong Sun; Kim, Dong-Yi; Koh, Yang-Suk; Jeung, Kyung Woon; Lee, Kyung‐Hwa; Lee, Ji-Shin; Juhng, Sang Woo; Lee, Jae-Hyuk

doi:10.1111/j.1440-1746.2007.05250.x

Cited by 57 publications

(49 citation statements)

References 43 publications

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“…Besides expressing mostly at the membrane, these three members of armidillo protein family were also found in the cytoplasm or nucleus. It has been shown to be important in the development of several tumors that constitutionally activated the Wnt/Wingless signaling pathway by stabilization and accumulation of β-catenin in the nucleus and cytoplasm [24][25][26][27] . Like β-catenin, γ-catenin can also bind to APC protein and is able to translocate into the nucleus participating in the Wnt signaling pathway [28] .…”

Section: Discussionmentioning

confidence: 99%

Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas

Zhai¹,

Yan²,

Li³

et al. 2008

WJG

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AIM:To examine the immunoreactivity of E-cadherin a n d fo u r s u b type s of c at e nin fami ly in human hepatocellular carcinomas (HCCs) and to investigate the correlation between expression of E-cadherin/ catenin complex and clinicopathologic parameters of HCC patients. METHODS: An immunohistochemical study for E-cadherin and catenins was performed on 97 formalin-fixed, paraffin-embedded specimens of HCC. RESULTS: Reduced expression of E-cadherin, α-, β-, γ-catenin and p120 was observed in 69%, 76%, 63%, 71% and 73%, respectively. Both expressions of E-cadherin and catenin components were significantly correlated with tumor grade (P = 0.000). It showed significant difference between expression of catenin members and tumor stage (P = 0.003, P = 0.017, P = 0.007 and P = 0.000, respectively). The reduced expression of E-cadherin in HCCs was significantly correlated with intrahepatic metastasis (IM) and capsular invasion (P = 0.008, P = 0.03, respectively).A close correlation was also observed between the expression of catenins and the tumor size (P = 0.002, P = 0.034, P = 0.016 and P = 0.000, respectively).In addition, the expression of each catenin was found correlated with IM (P = 0.012, P = 0.049, P = 0.026 and P = 0.014, respectively). No statistically significant difference was observed between the expression level of E-cadherin/catenin complex and lymph node permission, vascular invasion and satellite nodules. Interestingly, only expression of p120 showed correlation with AFP value (P = 0.035). The expression of E-cadherin was consistent with α-, β-, γ-catenin and p120 expression (P = 0.000). Finally, the abnormal expression of E-cadherin/catenin complex was significantly associated with patients' survival (P = 0.0253, P = 0.0052, P = 0.003, P = 0.0105 and P = 0.0016, respectively). Nevertheless, no component of E-cadherin/catenin complex was the independent prognostic factor of HCC patients. CONCLUSION: Down-regulated expressions of E-cadherin, catenins and p120 occur frequently in HCCs and contribute to the progression and development of tumor. It may be more exact and valuable to detect the co-expression of E-cadherin/catenin complex than to explore one of them in predicting tumor invasion, metastasis and patient's survival.

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Section: Discussionmentioning

confidence: 99%

Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas

Zhai¹,

Yan²,

Li³

et al. 2008

WJG

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“…Mutations in WNT signaling components (APC, β-catenin, AXIN, WTX, TCF4) can be the cause of WNT pathway activation in these tumors. [41][42][43][44][45] In colorectal cancer, mutations in WNT signaling components have been extensively characterized. Approximately 85% of colorectal tumors have mutations in APC, whereas an activating mutation in β-catenin was observed in 50% of colorectal tumors lacking APC mutations.…”

Section: Canonical Wnt Signalingmentioning

confidence: 99%

WNT signaling in glioblastoma and therapeutic opportunities

Lee

Ahn

et al. 2016

Laboratory Investigation

224

182

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WNTs and their downstream effectors regulate proliferation, death, and migration and cell fate decision. Deregulation of WNT signaling is associated with various cancers including GBM, which is the most malignant primary brain cancer. In this review, we will summarize the experimental evidence supporting oncogenic roles of WNT signaling in GBM and discuss current progress in the targeting of WNT signaling as an anti-cancer approach. In particular, we will focus on (1) genetic and epigenetic alterations that lead to aberrant WNT pathway activation in GBM, (2) WNT-mediated control of GBM stem cell maintenance and invasion, and (3) cross-talk between WNT and other signaling pathways in GBM. We will then review the discovery of agents that can inhibit WNT signaling in preclinical models and the current status of human clinical trials.

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“…Axin1 is constitutively expressed, whereas Axin2 (also known as Axil or Conductin) is induced by Wnt/β-catenin signalling and takes part in a negative feedback loop [75] . Kim et al [76] recently observed reduced Axin1 expression only in HCC tissues and not in cirrhotic nodules, implying that its reduced expression is independent of cirrhosis. There are currently no reports of Axin2 expression in HCC.…”

Section: Gsk3β Ckiα Axin and Apcmentioning

confidence: 99%

“…The TCF/LEF family has several spliced forms with unknown functional significance and it is suggested that they may activate preferential genes [86] . In HCC, mutations of TCF-4 are rare with 315 August 10, 2011|Volume 2|Issue 8| WJCO|www.wjgnet.com [70][71][72] phospho-GSK3β High 52 IHC [73] Axin1 Low 67 IHC [76] Dvl High 71 Western blotting [82] Prickle-1 Low 55 PCR [82] HDPR1 Low 58 PCR [83] PIN1 High 53 Western blotting [65] TCF-4 High 91 PCR [87] LEF-1 High 52 IHC [88] CDH17 High 72 IHC [90] CDH17: Cadherin-17; Dvl: Dishevelled; FZD: Frizzled; phospho-GSK3β: Phosphorylated glycogen synthase kinase 3β; HDPR1: Human homologue of Dapper; IHC: Immunohistochemistry; LEF: Lymphoid enhancer factor; PCR: Polymerase chain reaction; PIN1: Peptidyl-prolyl cis/trans isomerase; TCF: T-cell factor.…”

Section: Tcf/lefmentioning

confidence: 99%

Dickkopfs and Wnt/β-catenin signalling in liver cancer

Fatima¹

2011

WJCO

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Liver cancer is the fifth and seventh most common cause of cancer in men and women, respectively. Wnt/β-catenin signalling has emerged as a critical player in both the development of normal liver as well as an oncogenic driver in hepatocellular carcinoma (HCC). Based on the current understanding, this article summarizes the possible mechanisms for the aberrant activation of this pathway with specific focus on HCC. Furthermore, we will discuss the role of dickkopfs (DKKs) in regulating Wnt/β-catenin signalling, which is poorly understood and understudied. DKKs are a family of secreted proteins that comprise at least four members, namely DKK1-DKK4, which act as inhibitors of Wnt/β-catenin signalling. Nevertheless, not all members antagonize Wnt/β-catenin signalling. Their functional significance in hepatocarcinogenesis remains to be further characterized for which these studies should provide new insights into the regulatory role of DKKs in Wnt/β-catenin signalling in hepatic carcinogenesis. Because of the important oncogenic roles, there are an increasing number of therapeutic molecules targeting β-catenin and the Wnt/ β-catenin pathway for potential therapy of HCC. hepatocellular carcinoma anD the unmet meDical neeDSLiver cancer ranks the fifth most common cancer in men and the second leading cause of cancer-related death. In women, it is the seventh most frequent cancer and sixth leading cause of cancer death [1] . Hepatocellular carcinoma (HCC) is the most common primary malignancy of liver. Men are three times more likely to develop HCC than women and the incidence increases with age [2] . HCC is prevalent in Asia and Africa, but recently it is on the rise in the Western world due to an increase in hepatitis C virus (HCV) infection [3] . Risk factors for HCC include chronic hepatitis B virus (HBV) and HCV infections, cirrhosis, chronic alcohol abuse, aflatoxin ingestion, non-alcoholic steatohepatitis and other metabolic liver diseases [4,5] . Much of HCC occurs in the background of cirrhosis. About 80%-90% of patients with cirrhosis go on to develop HCC eventually and the remaining 10%-20% of cases develop HCC without cirrhosis. Furthermore, HBV and HCV infections increase the risk of developing cirrhosis and later HCC. Among the HCC

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Genetic alterations of Wnt signaling pathway–associated genes in hepatocellular carcinoma

Cited by 57 publications

References 43 publications

Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas

Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas

WNT signaling in glioblastoma and therapeutic opportunities

Dickkopfs and Wnt/β-catenin signalling in liver cancer

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