Effects of contactin-associated protein-like 2 on the proliferation,migration,and invasion of pituitary adenoma cells
WANG Qingsong
XIA Ying
Abstract：Objective To investigate the expression of contactin-associated protein-like 2(CNTNAP2)in pituitary adenoma cells,its effects on cell proliferation,migration,and invasion,and to elucidate the role of the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway in this process.Methods The expression level of CNTNAP2 in mouse pituitary adenoma cell lines was detected using real-time quantitative PCR(RT-qPCR)and Western blot.In pituitary adenoma GT1-1 cells transfected with CNTNAP2 overexpression plasmid(OE-CNTNAP2)and negative control plasmid(OE-NC),or CNTNAP2 small interfering RNA(si-CNTNAP2)and negative control sequence(si-NC),cell viability,apoptosis,migration,and invasion capabilities were assessed using the Cell Counting Kit-8(CCK-8),Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL),and Transwell assays,respectively.Western blot was performed to analyze the expression levels of apoptosis-and epithelial-mesenchymal transition(EMT)-related proteins,as well as the phosphorylation levels of PI3K/Akt.The PI3K/Akt pathway agonist 740 Y-P was used to treat the cells to investigate whether this pathway mediates the regulatory effects of CNTNAP2.Results The expression of CNTNAP2 was significantly lower in mouse pituitary adenoma cells than in normal pituitary cells.In the OE-CNTNAP2 group,cells overexpressing CNTNAP2 exhibited the following significant biological changes:inhibition of cell proliferation(CCK-8 assay showed decreased cell viability),increased apoptosis(elevated TUNEL-positive rate,upregulation of pro-apoptotic proteins Bax and cleaved caspase-3,and downregulation of anti-apoptotic protein Bcl-2),reduced migration and invasion capabilities(decreased number of transmembrane cells in Transwell assays),and suppression of EMT(upregulation of the epithelial marker E-cadherin and downregulation of the mesenchymal marker N-cadherin).Concurrently,the activity of the PI3K/Akt signaling pathway was inhibited in this group,as evidenced by reduced phosphorylation levels of PI3K and Akt.Conversely,in the si-CNTNAP2 group,cells with CNTNAP2 knockdown displayed the opposite biological phenotypes:enhanced proliferation,reduced apoptosis,improved migration and invasion capabilities,and promoted EMT,accompanied by activation of the PI3K/Akt signaling pathway.Treatment with 740 Y-P effectively reversed the effects induced by CNTNAP2 overexpression,including the inhibition of cell proliferation,increased apoptosis,reduced migration and invasion capabilities,and decreased phosphorylation levels of the PI3K/Akt pathway.Conclusion CNTNAP2 functions as a tumor suppressor in pituitary adenoma cells.Its overexpression inhibits the PI3K/Akt signaling pathway,thereby suppressing cell proliferation,migration,invasion,and the EMT process.
Keywords：pituitary adenomacontactin-associated protein-like 2proliferationmigration and invasion
Publication Date：2026-01-28
Online Publishing Date：2026-03-18(First online date of this platform, not the publication date of the document)
Pages：7( 9-15 )