Engulfment and cell motility 1 promotes tumor progression via the modulation of tumor cell survival in gastric cancer

Abstract

Background/aim: Engulfment and cell motility 1 (ELMO1) protein has been implicated in phagocytosis of apoptotic cells, cell migration, neurite outgrowth, cancer cell invasion and metastasis, and poor prognosis in various cancers. We investigated the role of ELMO1 in mediating the oncogenic behavior of gastric cancer (GC) cells. We also investigated the correlation between expression of ELMO1 in GC tissues and various clinicopathological parameters. Methods: We studied the impact of ELMO1 on tumor cell behavior using the pcDNA myc vector and small interfering RNA in AGS and SNU1750 GC cell lines. We performed western blotting and immunohistochemistry to investigate the expression of ELMO1 in GC cells and tissues. Results: ELMO1 overexpression inhibited apoptosis via the modulation of PARP, caspase-3 and caspase-7 in GC cells. ELMO1 overexpression led to significant increase in the number of migrating and invading GC cells. The expression of beta-cadherin decreased and that of Snail increased in GC cells upon ELMO1 overexpression. Phosphorylation of PI3K/Akt and GSK-3 beta was increased and that of beta-catenin was decreased upon ELMO1 overexpression in GC cells. These results were reversed after ELMO1 knockdown. ELMO1 expression was significantly associated with tumor size, cancer stage, lymph node metastasis and survival. ELMO1-positive tumors had significantly higher mean of Ki-67 labeling index than ELMO1 negative tumors. There was no significant relationship between ELMO1 expression and the mean value of the apoptotic index. Conclusions: Our results indicate that ELMO1 promotes tumor progression by modulating tumor cell survival in human GC.