Sustained JNK1 activation is associated with altered histone H3 methylations in human liver cancer

Chang, Qingshan; Zhang, Yadong; Beezhold, Kevin; Bhatia, Deepak; Zhao, Hongwen; Chen, Jianguo; Castranova, Vince; Shi, Xianglin; Chen, Fei

doi:10.1016/j.jhep.2008.07.037

Cited by 115 publications

(102 citation statements)

References 52 publications

(58 reference statements)

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“…Over half of human HCC samples show over-activated JNK1 (Hui et al, 2008). Sustained JNK1 expression in human HCC contributes to altered histone H3 methylation, which enhances the expression of genes regulating cell growth (Chang et al, 2009). Using inflammation-associated mouse HCC models, it was confirmed that JNK1 promotes tumor cell proliferation, probably due to the elevated expression of the cell cycle inhibitor p21 and the reduced expression of c-Myc (Hui et al, 2008).…”

Section: Jnks In Inflammation and Cancermentioning

confidence: 99%

MAPK signaling in inflammation-associated cancer development

2010

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Mitogen-activated protein (MAP) kinases comprise a family of protein-serine/threonine kinases, which are highly conserved in protein structures from unicellular eukaryotic organisms to multicellular organisms, including mammals. These kinases, including ERKs, JNKs and p38s, are regulated by a phosphorelay cascade, with a prototype of three protein kinases that sequentially phosphorylate one another. MAPKs transduce extracellular signals into a variety of cellular processes, such as cell proliferation, survival, death, and differentiation. Consistent with their essential cellular functions, MAPKs have been shown to play critical roles in embryonic development, adult tissue homeostasis and various pathologies. In this review, we discuss recent findings that reveal the profound impact of these pathways on chronic inflammation and, particularly, inflammation-associated cancer development.

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Section: Jnks In Inflammation and Cancermentioning

confidence: 99%

MAPK signaling in inflammation-associated cancer development

2010

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“…In recent years, studies have shed light on the clinical implications of signalling pathways in HCC, including the Ras/Raf/MEK/ERK pathway [16] , the PI3K/Akt/mTOR pathway [17] , the JNK pathway [18] and the NF-κB pathway [19] . A promising approach would be to identify molecular pathways responsible for initiating and sustaining HCC as targets for HCC therapy.…”

Section: Hepatocellular Carcinoma and The Unmet Medical Needsmentioning

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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“…128,129 More recently, definitive evidence has revealed a significant relationship between sustained JNK activation and the development of HCC. [129][130][131][132] JNK1 is overactivated in more than 50% of human HCC samples. [129][130][131][132] In one study, 56% of HCC tissue samples demonstrated elevated JNK1 activity relative to the case-matched noncancerous liver tissue.…”

mentioning

confidence: 99%

“…[129][130][131][132] JNK1 is overactivated in more than 50% of human HCC samples. [129][130][131][132] In one study, 56% of HCC tissue samples demonstrated elevated JNK1 activity relative to the case-matched noncancerous liver tissue. 131 This finding was supported by immunoblotting studies which demonstrated highly active JNK1 in about 55% of human HCC samples.…”

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confidence: 99%

Nonalcoholic fatty liver disease and hepatocellular carcinoma: A weighty connection

2010

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Hepatocellular carcinoma (HCC) is a common and deadly malignancy that is increasing in incidence in developed countries. The emergence of hepatitis C virus (HCV) accounts for about half of this increase in HCC, although the etiology of HCC in 15%-50% of new HCC cases remains unclear. The most common form of chronic liver disease in developed countries is nonalcoholic fatty liver disease (NAFLD), which encompasses a broad spectrum of histopathology. The prevalence of NAFLD, including the more aggressive nonalcoholic steatohepatitis (NASH), is increasing with the growing epidemics of diabetes and obesity. NASH can progress to cirrhosis and its related complications. Growing evidence suggests that NASH accounts for a large proportion of idiopathic or cryptogenic cirrhosis, which is associated with the typical risk factors for NASH. HCC is a rare, although important complication of NAFLD. Diabetes and obesity have been established as independent risk factors for the development of HCC. New evidence also suggests that hepatic iron deposition increases the risk of HCC in NASH-derived cirrhosis. Multiple case reports and case reviews of HCC in the setting of NASH support the associations of diabetes and obesity with the risk of HCC, as well as suggest age and advanced fibrosis as significant risks. Insulin resistance and its subsequent inflammatory cascade that is associated with the development of NASH appear to play a significant role in the carcinogenesis of HCC. The complications of NASH, including cirrhosis and HCC, are expected to increase with the growing epidemic of diabetes and obesity.

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Sustained JNK1 activation is associated with altered histone H3 methylations in human liver cancer

Cited by 115 publications

References 52 publications

MAPK signaling in inflammation-associated cancer development

MAPK signaling in inflammation-associated cancer development

Dickkopfs and Wnt/β-catenin signalling in liver cancer

Nonalcoholic fatty liver disease and hepatocellular carcinoma: A weighty connection

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