title: Helicobacter pylori promotes invasion and metastasis of gastric cancer cells through activation of AP-1 and up-regulation of CACUL1.
abstract: Infection with Helicobacter pylori is important in the development and progression of gastric cancer. However, the mechanisms that regulate this activation in gastric tumors remain elusive. CACUL1 has been cloned and identified as a novel gene that is expressed in many types of cancer and is involved in cell cycle regulation and tumor growth. The current study aimed to examine the expression of CACUL1 in gastric cancer samples and analyze its correlation with H. pylori infection. We found that CACUL1 was highly expressed in gastric cancer tissues and negatively correlated with gastric cancer differentiation and TNM stage. In addition, CACUL1 expression was high in H. pylori-infected tissues compared with H. pylori non-infected tissue. We found that H. pylori could up-regulate CACUL1 expression through activating protein 1. The up-regulation of CACUL1 expression could promote matrix metalloproteinase 9 and Slug expression to increase invasion and metastasis of tumor cells. These results suggested that H. pylori-triggered CACUL1 production occurred in an activating protein 1-dependent manner and regulated matrix metalloproteinase 9 and Slug expression to affect the invasion and metastasis of tumor cells. Therefore, CACUL1 is a potential therapeutic target for the treatment of aggressive gastric cancer.
authors.affiliation: Department of Oncology, First Hospital of Xi'an Jiaotong University, No. 277 YanTa West Road, Xi'an, Shaanxi 710061, PR China. Electronic address: yingkong76@gmail.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Kong
authors.forename: Li-qing
authors.initials: LQ
authors.lastname: Ma
authors.forename: Pei-song
authors.initials: PS
authors.lastname: Bai
authors.forename: Rong
authors.initials: R
authors.lastname: Da
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Xiao-gai
authors.initials: XG
authors.lastname: Qi
authors.forename: Jie-qun
authors.initials: JQ
authors.lastname: Ma
authors.forename: Ru-ming
authors.initials: RM
authors.lastname: Zhao
authors.forename: Nan-zheng
authors.initials: NZ
authors.lastname: Chen
authors.forename: Ke-jun
authors.initials: KJ
authors.lastname: Nan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D045744:Cell Line, Tumor; D044842:Cullin Proteins / Q000235:genetics* / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics / Q000382:microbiology* / Q000473:pathology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000873:Anthracenes; C546534:CACUL1 protein, human; D044842:Cullin Proteins; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; C432165:pyrazolanthrone; D020780:Matrix Metalloproteinase 9; D003474:Curcumin
keywords: AP-1; CACUL1; Gastric cancer; Helicobacter pylori; Metastasis