Molecular basis of gastric cancer development and progression

Zheng, Leizhen; Wang, Liwei; Ajani, Jaffer A.; Xie, Keping

doi:10.1007/s10120-004-0277-4

Cited by 162 publications

(131 citation statements)

References 193 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…The tumorigenesis process of gastric cancer has been widely studied. Besides environmental factors (Chyou et al, 1990;Nomura et al, 1990;Parsonnet et al, 1991;Tsugane and Sasazuki, 2007;Suzuki et al, 2009;Polk and Peek, 2010), genetic alterations of oncogenes, tumor-suppressor genes, cell cycle regulators, cell adhesion molecules and DNA repair genes have been identified to contribute to development or progression of gastric cancer (Wu et al, 1997;Zheng et al, 2004;Stock and Otto, 2005). The gene instability in gastric cancer including gene amplification, loss of heterozygosity (Sano et al, 1991) or microsatellite instability (Fang et al, 2003) may cause the inactivation of some tumor-suppressor genes, such as p53, and deregulation of some signaling molecules so as to enhance some signaling pathways, such as Wnt or Ras-dependent mitogen-activated protein kinase (MAPK) pathway, which may promote the tumorigenesis (Kim et al, 1991;Clements et al, 2002;Stock and Otto, 2005).…”

Section: Introductionmentioning

confidence: 99%

RUNX3-mediated transcriptional inhibition of Akt suppresses tumorigenesis of human gastric cancer cells

et al. 2012

View full text Add to dashboard Cite

Activation of Akt signaling pathway has been suggested involving in chemoresistance, metastasis and tumorigenesis of gastric cancer. However, the mechanism of Akt regulation in gastric cancer is not fully understood. RUNX3, which was first identified as a transcription factor, suppresses gastric tumorigenesis through regulating expression of target genes. Here, we found that restoration of RUNX3 significantly downregulates the protein and mRNA expression of Akt1 in gastric cancer cell lines, AGS and SNU-1. Knockdown of RUNX3 upregulates protein and mRNA expression of Akt1 in normal gastric epithelial cell line, GES-1. The negative correlation of RUNX3 and Akt expression and downstream b-catenin/cyclin D1 effectors was further confirmed in AGS and GES-1 cell lines, as well as clinical specimens of gastric cancer. We identified two RUNX3-binding sites in Akt1 promoter and the binding of RUNX3 on Akt1 promoter significantly inhibits Akt1 expression. The RUNX3-mediated inhibition of Akt1 caused b-catenin protein degradation and then cyclin D1 downregulation. Restoration of cyclin D1 reverses cell growth inhibition and G1 phase arrest induced by RUNX3 in gastric cancer cells. Our results show that loss of RUNX3 expression can enhance the Akt1-mediated signaling pathway and promote the tumorigenesis process in human gastric cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

RUNX3-mediated transcriptional inhibition of Akt suppresses tumorigenesis of human gastric cancer cells

et al. 2012

View full text Add to dashboard Cite

show abstract

“…It is the most common epithelial malignancy and is the leading cause of cancer-related death in Asia and in parts of South America. It remains the second most frequently diagnosed malignancy worldwide and is a cause of 12% of all cancer-related deaths each year 1,2 .…”

Section: Introductionmentioning

confidence: 99%

Claudin-1 Has Tumor Suppressive Activity and Is a Direct Target of RUNX3 in Gastric Epithelial Cells

Chang

Ito

et al. 2010

Gastroenterology

View full text Add to dashboard Cite

“…Despite these reports, inconsistent results exist among the different studies, and the reported parameters provide limited information on the prognosis of individual patients because of the complex biology of the disease. 8 In this study, we attempted to screen for proteins that can be used for diagnosis and prognosis of gastric cancer using the Protein Pathway Array method, a multiplex immunoblot-based assay combined with computational analysis. 9 The Protein Pathway Array is a novel proteomic method that can characterize hundreds of proteins in clinical samples and identify alterations in protein expression or abundance with biomarker potential.…”

mentioning

confidence: 99%

Protein Signatures for Classification and Prognosis of Gastric Cancer

Wang¹,

Ye²,

Sun³

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Current methods have limited accuracy in predicting survival and stratifying patients with gastric cancer for appropriate treatment. We sought to identify protein signatures of gastric cancer for classification and prognostication. The Protein Pathway Array (initial study) and Western blot (confirmation) were used to assess the protein expression in a total of 199 fresh frozen gastric samples. There were 56 paired samples divided into a training set (n ‫؍‬ 37) and a validation set (n ‫؍‬ 19) for the identification of differentially expressed proteins between tumor and normal tissues. There were 56 tumor samples used to identify proteins correlating with tumor and nodal staging. All 93 tumor samples were used to identify candidate proteins for predicting survival. We confirmed the survival prediction of the candidate proteins by using an additional cohort of gastric cancer samples (n ‫؍‬ 50). There were 22 proteins differentially expressed between normal and tumor tissues. Nine proteins were selected to build the predictor to classify normal and tumor samples. Ten proteins were differentially expressed among different T stages and four of these were associated with invasive behavior. An additional four proteins were associated with lymph node metastasis. Two proteins were identified as independent risk factors for overall survival. This study indicated that some dysregulated signaling proteins could be selected Gastric cancer is the fourth most common malignancy and ranked as the second leading cause of cancer death worldwide.1 The geographic distribution of incidence and mortality of gastric cancer varies remarkably worldwide. Areas with high incidence include Japan, Korea, China, Eastern Europe, and parts of Latin America. The mortality of gastric cancer has declined in past decades, mainly due to early detection by gastric endoscopy. 2 However, unlike that of other common cancers, the prognosis for most gastric cancer is poor and has improved little for the past several decades. Despite recent advances in chemotherapy and surgical techniques, the overall 5-year survival rate is lower than 40%.3 Perplexingly, the prognosis varies widely in patients with stage II or III disease for undetermined biological reasons.

show abstract

Molecular basis of gastric cancer development and progression

Cited by 162 publications

References 193 publications

RUNX3-mediated transcriptional inhibition of Akt suppresses tumorigenesis of human gastric cancer cells

RUNX3-mediated transcriptional inhibition of Akt suppresses tumorigenesis of human gastric cancer cells

Claudin-1 Has Tumor Suppressive Activity and Is a Direct Target of RUNX3 in Gastric Epithelial Cells

Protein Signatures for Classification and Prognosis of Gastric Cancer

Contact Info

Product

Resources

About