Dataset Information

G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner.

ABSTRACT: Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and metastasis. Moreover, we observed that Reg IV induced G9A via the p-ERK/p-SP1 pathway. SP1 directly binds the G9A promoter and enhances G9A expression, and upregulated G9A then forms a transcriptional activator complex with P300 and GR, thereby promoting ITGB3 expression induced by dexamethasone (DEX) and contributing to GC metastasis. However, the G9A-mediated increase in ITGB3 expression was not dependent on the SET domain and methyltransferase activity of G9A. This study demonstrates that G9A is an independent prognostic marker and promotes metastasis in GC, thus suggesting that it may be a tumor biomarker and potential therapeutic target in GC.

SUBMITTER: Hu L

PROVIDER: S-EPMC5833452 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner.

Hu Lei L Zang Ming-de MD Wang He-Xiao HX Zhang Bao-Gui BG Wang Zhen-Qiang ZQ Fan Zhi-Yuan ZY Wu Huo H Li Jian-Fang JF Su Li-Ping LP Yan Min M Zhu Zhi-Qiang ZQ Yang Qiu-Meng QM Huang Qiang Q Liu Bing-Ya BY Zhu Zheng-Gang ZG

Cell death & disease 20180215 3

Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and metast ...[more]

PMID: 29449539

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Project description:BACKGROUND:VEGF/VEGFR2 pathway is the central therapeutic target in anti-angiogenic treatment in multiple cancers. However, little work has been carried out concerning the pro-malignancy functions of VEGFR2 that are independent of its pro-angiogenesis effects in gastric cancer. Here, we demonstrated that VEGFR2 up-regulation in gastric cancer tissues was a prognostic marker for poor disease-free survival and overall survival of gastric cancer patients. METHODS:Immunohistochemistry was used to detect VEGFR2 and VTN expressions in specimens. Kaplan-Meier curves were constructed for survival analysis. Stably knockdown cell lines and overexpression cell lines were constructed by small interfering RNA and plasmids transfection. Real-time PCR and Western blot were used to confirm the expressions of target genes at both RNA and protein levels. Cell proliferation was measured by using Cell Counting Kit-8 and xenograft models. Microarray and bioinformatic analysis were also performed to identify the relationship between Vitronectin (VTN) and VEGFR2. RESULTS:When overexpressed in gastric cancer cells, VEGFR2 increased cellular proliferation and invasion in vitro and tumor formation in xenograft models. By using integrating microarray and bioinformatic analysis, we identifiedVTN as a downstream of VEGFR2 pathway. In gain- and loss-of function analysis in gastric cancer cells, VTN was further verified in consistent with VEGFR2 in expression levels and in regulating cell growth and motility in vitro and in vivo. Moreover, in gastric cancer samples, VTN was as also revealed as a poor prognostic factor. CONCLUSIONS:Our present findings defined a novel activity for VEGFR2 in promoting tumorogenicity, motility and indicating a poor survival in gastric cancer beyond its known pro-angiogenic effects. IMPLICATIONS:Our present findings defined a novel activity for VEGFR2 in promoting tumorogenicity, motility and indicating a poor survival in gastric cancer beyond its known pro-angiogenic effects, which may provide a new and valuable target for design of therapies for intervention and a new cognitive perspective for the anti-angiogenesis therapies.

Dataset Information

G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner.

Publications

G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner.

Similar Datasets

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