Dataset Information

JP3, an antiangiogenic peptide, inhibits growth and metastasis of gastric cancer through TRIM25/SP1/MMP2 axis.

ABSTRACT:

Background

Gastric cancer (GC) is the most prevalent gastrointestinal tumor with an unfavorable clinical prognosis. GC patients are largely threatened owing to metastasis and drug resistance. Tumor angiogenesis plays an important role in the development of gastric cancer and is a challenge in the treatment of gastric cancer.

Methods

Mouse xenograft models were used for screening of therapeutic peptides on GC growth and metastasis. Routine laboratory experimental methods including conditional cell culture, tube formation assay, qRT-PCR, Western blotting, immunohistochemistry (IHC), ubiquitination assay, and immunofluorescence (IF) were used in mechanism investigation; protein docking analysis and coimmunoprecipitation (Co-IP) were used for prediction and confirmation of interactions between JP3/SP1 and TRIM25/MEK1/2.

Results

We identified an MMP2-targeted peptide JP3 that plays inhibiting roles in modulating growth and metastasis of GC in vivo and has no observable toxic side effects. JP3 reduced tumor microvessel density (MVD) in vivo and human umbilical vein endothelial cells (HUVECs) tube formation in vitro. Mechanistic studies revealed that JP3 reduces polyubiquitination-mediated degradation of TRIM25 by increasing the stability of TRIM25 through phosphorylating it at Ser12. TRIM25, as an E3 ubiquitin ligase, promoted the ubiquitin of SP1 at K610, further suppressed expression of MMP2 and inhibited angiogenesis in GC. Importantly, the inversely association between TRIM25 and SP1 protein level was further verified in human GC tissues. Decreased TRIM25 expression and increased SP1 expression in tumor tissues were positively correlated with poor prognosis of GC patients.

Conclusions

MMP2-targeted peptide JP3 plays a therapeutic role in GC through anti-angiogenesis by modulating TRIM25/SP1/MMP2.

SUBMITTER: Chen JJ

PROVIDER: S-EPMC7310436 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

JP3, an antiangiogenic peptide, inhibits growth and metastasis of gastric cancer through TRIM25/SP1/MMP2 axis.

Chen Jun-Jie JJ Ren Yan-Lin YL Shu Chuan-Jun CJ Zhang Yi Y Chen Min-Juan MJ Xu Jin J Li Jin J Li Ai-Ping AP Chen Dong-Yin DY He Jing-Dong JD Shu Yong-Qian YQ Zhou Jian-Wei JW

Journal of experimental & clinical cancer research : CR 20200623 1

<h4>Background</h4>Gastric cancer (GC) is the most prevalent gastrointestinal tumor with an unfavorable clinical prognosis. GC patients are largely threatened owing to metastasis and drug resistance. Tumor angiogenesis plays an important role in the development of gastric cancer and is a challenge in the treatment of gastric cancer.<h4>Methods</h4>Mouse xenograft models were used for screening of therapeutic peptides on GC growth and metastasis. Routine laboratory experimental methods including ...[more]

PMID: 32576271

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Dataset Information

JP3, an antiangiogenic peptide, inhibits growth and metastasis of gastric cancer through TRIM25/SP1/MMP2 axis.

Background

Methods

Results

Conclusions

Publications

JP3, an antiangiogenic peptide, inhibits growth and metastasis of gastric cancer through TRIM25/SP1/MMP2 axis.

Similar Datasets

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