RUNX3 directly interacts with intracellular domain of Notch1 and suppresses Notch signaling in hepatocellular carcinoma cells

Gao, Juan; Chen, Yu; Wu, Kaichun; Liu, Jie; Zhao, Yanli; Pan, Yanglin; Du, Rui; Guo, Zheng; Xiong, Yimin; Xu, Hualin; Fan, Daiming

doi:10.1016/j.yexcr.2009.09.025

Cited by 60 publications

(41 citation statements)

References 45 publications

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“…RUNX3 expression in Stage IIA esophageal cancer was also found to be signifi¬cantly associated with poor prognosis factors, such as T-status. These results fit nicely with the previous studies, which revealed that the low expression of RUNX3 in primary gastric cancer was associated with a significantly shorter survival (Gao et al, 2010).…”

Section: 5169 Effects Of Adjuvant Chemotherapy On Survival After Lymsupporting

confidence: 92%

Retrospective Study of Adjuvant Chemotherapy Effects on Survival Rate after Three-Field Lymph Node Dissection for Stage IIA Esophageal Cancer

Chen

Wang²

2015

Asian Pacific Journal of Cancer Prevention

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To determine the efficacy of postoperative adjuvant chemotherapy with paclitaxel plus cisplatin (Taxol + DDP, TP therapy) for stage IIA esophageal squamous cell carcinoma (ESCC) and to investigate the expression of RUNX3 in lymph node metastasis-negative esophageal cancer and its relationship with medical prognosis, a retrospective summary of clinical treatment of 143 cases of stage IIA esophageal squamous cell carcinoma patients was made. The patients were divided into two groups, a surgery alone control group (52 patients) and a chemotherapy group that received postoperative TP therapy (91 patients). The disease-free and 5 year survival rates were compared between the groups and a multivariate analysis of prognostic factors was performed. The same analysis was performed for cases classified as RUNX3 positive and negative, with post-operative specimens assessed by immunohistochemistry. Although the disease-free and 5 year survival rates in control and chemotherapy groups did not significantly differ and there was no significance in RUNX3 negative cases, postoperative adjuvant chemotherapy in the chemotherapy group was shown to improve disease-free and 5 year survival rate compared to the control group in RUNX3 positive cases. On Cox regression multivariate analysis, postoperative adjuvant chemotherapy (P<0.01) was an independent prognostic factor for RUNX3 positive cases, suggesting that postoperative TP may be effective as adjuvant chemotherapy for stage IIA esophageal cancer patients with RUNX3 positive lesions.

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Section: 5169 Effects Of Adjuvant Chemotherapy On Survival After Lymsupporting

confidence: 92%

Retrospective Study of Adjuvant Chemotherapy Effects on Survival Rate after Three-Field Lymph Node Dissection for Stage IIA Esophageal Cancer

Chen

Wang²

2015

Asian Pacific Journal of Cancer Prevention

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“…28 In addition, as an important downstream target of transforming growth factor beta (TGFb) superfamily signaling, RUNX3 acts as a tumor suppressor by regulating a series of cancer-related genes, such as tumor protein 53 (p53), 29 cyclin-dependent kinase inhibitor 1A (P21), 30 AT motif-binding factor 1 (ATBF1), 31 notch 1 (Notch), 32 cyclin-dependent kinase inhibitor 1B (P27), and Caspace3. 33 Some studies have indicated that loss of RUNX3 contributes to hyperplasia and intestinal metaplasia of gastric mucosa epithelial cells in an animal model, 34 whereas the restoration of RUNX3 activated the apoptotic pathway in GC.…”

Section: Introductionmentioning

confidence: 99%

Stepwise cumulation of RUNX3 methylation mediated by Helicobacter pylori infection contributes to gastric carcinoma progression

Liu

et al. 2012

Cancer

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BACKGROUND: Helicobacter pylori has been recognized as a definite carcinogen for gastric cancer (GC); however, the pathogenesis of H. pylori infection remains unclear. Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene whose deficiency is causally related to GC. However, in H. pylori infection-associated GC, the role of RUNX3 has not been studied. METHODS: The authors used real-time methylation-specific polymerase chain reaction analysis to determine methylation status of the RUNX3 promoter in a spectrum of gastric lesions, including 220 samples of chronic atrophic gastritis, 196 samples of intestinal metaplasia, 134 samples of gastric adenoma, 102 samples of dysplasia, and 202 samples of GC with paired noncancerous mucosa tissues and corresponding blood specimens. The association of abnormal methylation with precancerous gastric lesions was evaluated along with the association between RUNX3 methylation and H. pylori infection, and the concordance of methylation levels was investigated between serum and tissues. RESULTS: The results indicated that increasing RUNX3 promoter methylation was correlated with distinct stages of GC progression. GC tissues had the highest methylation proportion (75.2%) compared with precancerous gastric lesions, including chronic atrophic gastritis (15.9%), intestinal metaplasia (36.7%), gastric adenoma (41.8%), and dysplasia (54.9%). H. pylori infection, a major risk factor for GC, contributed to the inactivation of RUNX3 in gastric epithelial cells through promoter hypermethylation. The levels of RUNX3 methylation in serum were in significant concordance with the methylation levels observed in GC tissues (P ¼ .887). CONCLUSIONS: The current findings supported RUNX3 methylation as a risk factors for the carcinogenesis of chronic atrophic gastritis with H. pylori infection and indicated that circulating RUNX3 methylation is a valuable biomarker for the detection of early GC.

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“…Additionally, Notch signaling is crucial for the differentiation of hepatocytes into biliary lineage cells during the early stages of ICC developments. Gain and loss of function studies have demonstrated that ICC develops via the Notch-mediated differentiation of hepatocytes into biliary lineage cells, and that the malignancy and progression of the tumor are dependent on the intensity of Notch signaling in hepatocytes (74). Notably, hepatitis-infected hepatocytes may be converted into biliary lineage cells via Notch signal activation and thus become the point of origin for ICC (75).…”

Section: Role Of Notch In Hcc and Icc Developmentmentioning

confidence: 99%

Oncogenic role of the Notch pathway in primary liver cancer

et al. 2016

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Abstract. Primary liver cancer, which includes hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and fibrolamellar HCC, is one of the most common malignancies and the third leading cause of cancer-associated mortality, worldwide. Despite the development of novel therapies, the prognosis of liver cancer patients remains extremely poor. Thus, investigation of the genetic background and molecular mechanisms underlying the development and progression of this disease has gained significant attention. The Notch signaling pathway is a crucial determinant of cell fate during development and disease in several organs. In the liver, Notch signaling is involved in biliary tree development and tubulogenesis, and is also significant in the development of HCC and ICC. These findings suggest that the modulation of Notch pathway activity may have therapeutic relevance. The present review summarizes Notch signaling during HCC and ICC development and discusses the findings of recent studies regarding Notch expression, which reveal novel insights into its function in liver cancer progression.

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RUNX3 directly interacts with intracellular domain of Notch1 and suppresses Notch signaling in hepatocellular carcinoma cells

Cited by 60 publications

References 45 publications

Retrospective Study of Adjuvant Chemotherapy Effects on Survival Rate after Three-Field Lymph Node Dissection for Stage IIA Esophageal Cancer

Retrospective Study of Adjuvant Chemotherapy Effects on Survival Rate after Three-Field Lymph Node Dissection for Stage IIA Esophageal Cancer

Stepwise cumulation of RUNX3 methylation mediated by Helicobacter pylori infection contributes to gastric carcinoma progression

Oncogenic role of the Notch pathway in primary liver cancer

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