Inactivation of RUNX3 by Helicobacter pylori and gastric cancer

幽门螺杆菌导致 RUNX3 失活与胃癌

• 批准号: 8485602
• 负责人: Lin-Feng Chen
• 金额: $ 18.32万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8485602
• 关键词: Address; Animal Experiments; Biological Models; Cancer Etiology; Cells; Cessation of life; Complex; Cultured Cells; Cytosol; Data; Development; Developmental Process; Down-Regulation; Elements; Epithelial Cells; Event; Gastric Adenocarcinoma; Gene Expression; Gerbils; Goals; Helicobacter Infections; Helicobacter pylori; In Vitro; Infection; Lead; Malignant Neoplasms; Mediating; Molecular; Neoplasm Metastasis; Nuclear Export; Pathogenesis; Physiological; Play; Prevention; Recruitment Activity; Risk Factors; Role; Second Primary Cancers; Staging; Stomach; Stomach Diseases; Transcription Factor 3; Tumor Suppressor Proteins; Ubiquitination; Virulence Factors; base; cancer diagnosis; carcinogenesis; in vivo; inhibitor/antagonist; insight; malignant stomach neoplasm; mutant; outcome forecast; pathogen; prevent; response; transcription factor; ubiquitin-protein ligase

DESCRIPTION (provided by applicant): Runt-related transcription factor 3, or RUNX3, is a tumor suppressor in gastric cancer. Inactivation of RUNX3 is causally associated with the genesis of gastric cancer, since RUNX3 is frequently inactivated in gastric cancers. Infection with Helicobacter pylori is the strongest risk factor for the development of gastric cancer. Recent studies have indicated that H. pylori infection plays an important role in the inactivation of RUNX3, and that this inactivation contributes to the pathogenesis of H. pylori. We recently demonstrated that H. pylori inactivate RUNX3 by inducing its ubiquitination and degradation during an early stage of the infection in a virulence factor CagA-dependent manner. However, the detailed molecular mechanism and the physiological function of this inactivation in the development of gastric cancer remain unclear. The overall goal of this proposal is to investigate how H. pylori utilize CagA to inactivate RUNX3 and the contribution of this inactivation to the formation of gastric cancer. In Specific Aim 1, we will determine how H. pylori CagA induce the ubiquitination and degradation of RUNX3. We will investigate whether nuclear export of RUNX3 is a prerequisite for its degradation and identify the CagA-associated ubiquitin E3 ligase for RUNX3. In Specific Aim 2, we will determine how H. pylori CagA interact with RUNX3 and whether blocking the interaction could prevent the formation of H. pylori-induced gastric cancer. These cell-based and in vivo animal experiments will provide new insights into the role of H. pylori CagA in the pathogenesis of H. pylori and give a better understanding of the role RUNX3 plays as a tumor suppressor in gastric cancer.

描述（由申请人提供）：runt相关转录因子3 （RUNX3）是胃癌中的肿瘤抑制因子。RUNX3的失活与胃癌的发生有因果关系，因为RUNX3在胃癌中经常失活。幽门螺杆菌感染是胃癌发生的最大危险因素。最近

项目成果

Role of the Helicobacter pylori-induced inflammatory response in the development of gastric cancer.

• DOI: 10.1002/jcb.24389
• 发表时间: 2013-03
• 期刊: JOURNAL OF CELLULAR BIOCHEMISTRY
• 影响因子: 4
• 作者: Lamb, Acacia;Chen, Lin-Feng
• 通讯作者: Chen, Lin-Feng

Helicobacter pylori activates NF-κB by inducing Ubc13-mediated ubiquitination of lysine 158 of TAK1.

• DOI: 10.1002/jcb.24573
• 发表时间: 2013-10
• 期刊: JOURNAL OF CELLULAR BIOCHEMISTRY
• 影响因子: 4
• 作者: Lamb, Acacia;Chen, JinJing;Blanke, Steven R.;Chen, Lin-Feng
• 通讯作者: Chen, Lin-Feng