Overexpression of NCAPG inhibits cardia adenocarcinoma apoptosis and promotes epithelial-mesenchymal transition through the Wnt/β-catenin signaling pathway

Cardia adenocarcinoma (CA) is a distinct form of gastric cancer, and the optimal means of treating it remains controversial. At present, the role of the condensation complex gene non-SMC condensin I complex subunit G (NCAPG) in CA is uncertain, and as such the present study was designed to elucidate its importance in this oncogenic context.

NCAPG overexpression can promote EMT and suppress tumor cell apoptosis via the activation of Wnt/β-catenin signaling.

We first used bioinformatics approaches to assess NCAPG expression profiles in CA using public databases. Protein profiling was also used to examine the expression of this protein in CA tumors and adjacent tissues from 20 patients. Then the expression of NCAPG in CA samples was quantified via qRT-PCR and Western blotting. NCAPG knockdown and overexpression in the SGC-7901 and AGS cell lines were subsequently performed, after which the expression of key proteins associated with epithelial-mesenchymal transition (EMT; E-cadherin, vimentin, N-cadherin, Snail, Slug) and the regulation of apoptotic responses (caspase-3, Bax, Bcl-2) was measured. The mechanistic role of NCAPG in CA was additionally studied by analyzing proteins associated with Wnt/β-catenin signaling including Wnt1, phosphorylated GSK3β, β-catenin, and phosphorylated β- catenin. The impact of NCAPG on the migration, survival, and invasion of CA cells was further examined.

CA samples exhibited high NCAPG expression. When this gene was overexpressed in cell lines, it reduced caspase-3, Bax, and E-cadherin levels whereas it elevated Bcl-2, vimentin, N-cadherin, Snail, and Slug levels. NCAPG overexpression also resulted in the enhanced expression of Wnt1, phosphorylated GSK3β, and total β-catenin and the reduced expression of phosphorylated β-catenin. The knockdown of NCAPG, in contrast, yielded the opposite phenotype. At a functional level, the overexpression of NCAPG improved the apoptotic resistance of CA cells while driving them to undergo EMT and to become more invasive and migratory. Conclusions: NCAPG overexpression can promote EMT and suppress tumor cell apoptosis via the activation of Wnt/β-catenin signaling.