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Tumor Biology

, Volume 37, Issue 4, pp 5225–5230 | Cite as

Isocitrate dehydrogenase 2 inhibits gastric cancer cell invasion via matrix metalloproteinase 7

  • Dandan Wu
Original Article

Abstract

Isocitrate dehydrogenase 2 (IDH2) is a mitochondrial NADP-dependent isocitrate dehydrogenase and has been found to be a tumor suppressor in several types of tumors. However, the roles of IDH2 in hepatocellular carcinoma (GC) as well as underlying mechanisms remain unknown. Here, the IDH2 and matrix metalloproteinase 7 (MMP7) levels in the specimens from 30 GC patients were investigated by Western blot and ELISA, respectively. Their relationship was examined by correlation analyses. Patient survival with high IDH2 levels and low IDH2 levels was compared. IDH2 levels, and MMP7 levels were modified in a human GC cell line. The effects of IDH2 or MMP7 modulation on the expression of each other were analyzed. The dependence of nuclear factor κB (NF-κB) signaling was examined using a specific inhibitor. We found that the IDH2 levels significantly decreased in GC, and were even lower in GC with metastases, compared to those without metastases. IDH2 levels inversely correlated with MMP7 levels in GC. GC patients with low IDH2 had lower 5-year survival. MMP7 levels did not regulate IDH2 levels, while IDH2 inhibited MMP7 levels in GC cells, in a NF-κB signaling dependent manner. Together, these data suggest that IDH2 may be a tumor suppressor in that its loss may promote malignant progression of GC via NF-κB-dependent increases in MMP7 activity.

Keywords

Isocitrate dehydrogenase 2 (IDH2) NF-κB Matrix metalloproteinase 7 (MMP7) Gastric cancer (GC) Metastases 

Notes

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Gastroenterologythe First Affiliated Hospital of Liaoning Medical UniversityJinzhouChina

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