Stomatin-like protein 2 regulates survivin expression in non-small cell lung cancer cells through β-catenin signaling pathway

Abstract

The overexpression of stomatin-like protein-2 (SLP-2) is commonly observed in non-small cell lung cancer (NSCLC) cells. In the present study, we transfected a number of NSCLC cells with an SLP-2 shRNA-expressing vector (AdSLP2i) and examined its possible effects on cell growth and apoptosis. We found that suppression of SLP-2 expression inhibited cell growth, and that the apoptosis induced by SLP-2 suppression was correlated with decreased survivin protein expression. Moreover, the reduced survivin expression was found to be associated with reduced β-catenin nuclear localization and appeared not to be modulated through the AKT signaling pathway. By using immunoprecipitation and proteomics to analyze protein–protein interactions in A549 cells with SLP-2 overexpression, we found that annexin A2 interacted with SLP-2 and β-catenin directly. Our data further suggested that the knockdown of SLP-2 gene affected the SLP-2/Annexin A2/β-catenin cascade formation, reduced the translocation of cytoplasmic β-catenin into nucleus, and downregulated downstream target genes. The results presented in this study, together with our previous findings, suggest that SLP-2 promotes NSCLC cell proliferation by enhancing survivin expression mediated via β-catenin pathway.

ClC-2 knockdown prevents cerebrovascular remodeling via inhibition of the Wnt/β-catenin signaling pathway

“…We also noted that ClC-2 inhibition had no effect on AngII-induced HBVSMC proliferation after recombinant Wnt3a treatment, further supporting the critical role of the Wnt/β-catenin pathway in the impact of ClC-2. Upon β-catenin translocation, nuclear β-catenin facilitates the transcriptional activation of target genes in the nucleus, such as survivin and cyclin D1 [ 29 , 30 ]. These are both important regulators of the cell cycle.…”

Early Diagnostic and Prognostic Value of BIRC5 in Clear Cell Renal Cell Carcinoma Based on TCGA Data

“…Second, BIRC5 facilitates the invasion and migration of tumor cells mediated through the PI3K/AKT pathway [26] or the TGF-β pathway [27]. Another, it can regulate tumor cell proliferation mediated by theβ-catenin pathway [28]. These results may explain BIRC5 was mainly involved in the regulation of cell cycle and apoptosis.…”

Myricanol 5-fluorobenzyloxy ether regulation of survivin pathway inhibits human lung adenocarcinoma A549 cells growth in vitro

“…The role of apoptosis in anti-cancer is becoming increasingly important [23]. Therefore, the induction of tumor cell apoptosis associate with survivin pathway is an important mechanism for targeted cancer therapy [24,25]. In apoptosis, drugs inhibit the expression levels of survivin and XIAP genes, and Bcl-2 interacting mediator of cell death (BIM) domains of survivin and XIAP proteins can bind to the second mitochondrial activator of caspase (SMAC/DIABLO), antagonize SMAC/DIABLO apoptotic ability, and inhibit activated caspase-3, − 7, and − 9 to promote cell apoptosis [26].…”

“…The role of apoptosis in anti-cancer is becoming increasingly important [ 23 ]. Therefore, the induction of tumor cell apoptosis associate with survivin pathway is an important mechanism for targeted cancer therapy [ 24 , 25 ].…”