Previous studies have shown reduced expression of Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) and its tumor-suppressive role in gastric cancer (GC). However, the precise role of SHIP2 in the migration and invasion of GC cells remains unclear. Here, an IQ motif containing the GTPase-activating protein 2 (IQGAP2) as a SHIP2 binding partner, was screened and identified by co-immunoprecipitation and mass spectrometry studies. While IQGAP2 ubiquitously expressed in GC cells, IQGAP2 and SHIP2 co-localized in the cytoplasm of GC cells, and this physical association was confirmed by the binding of IQGAP2 to PRD and SAM domains of SHIP2. The knockdown of either SHIP2 or IQGAP2 promoted cell migration and invasion by inhibiting SHIP2 phosphatase activity, activating Akt and subsequently increasing epithelial–mesenchymal transition (EMT). Furthermore, knockdown of IQGAP2 in SHIP2-overexpressing GC cells reversed the inhibition of cell migration and invasion by SHIP2 induction, which was associated with the suppression of elevated SHIP2 phosphatase activity. Moreover, the deletion of PRD and SAM domains of SHIP2 abrogated the interaction and restored cell migration and invasion. Collectively, these results indicate that IQGAP2 interacts with SHIP2, leading to the increment of SHIP2 phosphatase activity, and thereby inhibiting the migration and invasion of GC cells via the inactivation of Akt and reduction in EMT.
Density functional theory and volume-based thermodynamics calculations were performed to study the effects of different substituents and linkages on the densities, heats of formation (HOFs), energetic properties, and thermodynamics of formation for a series of energetic nitrogen-rich salts composed of triaminoguanidinium cation and 5-nitroiminotetrazolate anions. The results show that the -NO(2), -NF(2), or -N(3) group is an effective substituent for increasing the densities of the 5-nitroiminotetrazolate salts, whereas the effects of the bridge groups on the density are coupled with those of the substituents. The substitution of the group -NH(2), -NO(2), -NF(2), -N(3), or the nitrogen bridge is helpful for increasing the HOFs of the salts. The calculated energetic properties indicate that the -NO(2), -NF(2), -N(3), or -N=N- group is an effective structural unit for improving the detonation performance for salts. The thermodynamics of formation of the salts show that all the salts may be synthesized easily by the proposed reactions. The structure-property relationships provide basic information for the molecular design of novel high-energy salts.
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