Abstract
Rap1GAP is a crucial tumor suppressor, but its role in gastric cancer (GC) is little investigated. In this study, we found that the expression of Rap1GAP was decreased in GC. Low expression of Rap1GAP was positively correlated with advanced pTNM stage, Borrmann types, tumor diameter and poor prognosis in patients with GC. Low expression of Rap1GAP correlated with loss of E-cadherin expression, and anomalous positivity of MMP2 expression. Multivariate analysis showed that low expression of Rap1GAP was an independent prognostic factor. Ectopic expression of Rap1GAP impaired cell migration and invasion, promoted the expression of E-cadherin and decreased the expression of MMP2. These results suggest that Rap1GAP functions as a novel suppressor of EMT and tumor metastasis in GC, and loss of Rap1GAP predicts poor prognosis in GC.
Highlights
RAP1 GTPase activating protein (Rap1GAP), a 663-amino-acid protein with a molecular weight of 73 kDa, is the first identified member of the family of GTPase-activating proteins (GAPs) [1, 2]
Low expression of Rap1GAP correlated with loss of E-cadherin expression, and anomalous positivity of Matrix metalloproteinase-2 (MMP2) expression
Impaired cell migration and invasion, promoted the expression of E-cadherin and decreased the expression of MMP2. These results suggest that Rap1GAP functions as a novel suppressor of Epithelial–mesenchymal transition (EMT) and tumor metastasis in gastric cancer (GC), and loss of Rap1GAP predicts poor prognosis in GC
Summary
Rap1GAP, a 663-amino-acid protein with a molecular weight of 73 kDa, is the first identified member of the family of GTPase-activating proteins (GAPs) [1, 2]. Thereafter, overexpression of Rap1GAP in cancer cells impairs cell migration and invasion in vitro [5, 6, 9, 13,14,15], and inhibits tumor formation and metastasis in vivo [6, 14, 16, 17]. Epithelial–mesenchymal transition (EMT) is a complex biological program in which epithelial cells undergo a dramatic morphological change and switch to form mesenchymal cells This switch occurs along with a reduction of epithelial marker proteins, such as. We explored the effect of Rap1GAP in vitro, and the corresponding changes in E-cadherin and MMP2 expression, and in migration and invasion capacity of GC cells. For E-cadherin (Table 1 and Figure 1C, 1F), and aberrant metastasis protein expression frequencies were 74.15%.
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