PTTG1 regulates the TGF-β/Smad pathway to promote the growth and metastasis of gastric cancer cells.

BACKGROUND: Pituitary tumor-transforming gene 1 (PTTG1) has been implicated in multiple malignancies; however, its precise role and regulatory mechanism in gastric cancer remain unclear. This study aimed to determine how PTTG1 regulates cell proliferation, migration, and epithelial-mesenchymal transition (EMT) through the TGF-β/Smad signaling pathway in gastric cancer. METHODS: PTTG1 expression in gastric cancer was evaluated using The Cancer Genome Atlas (TCGA) datasets and subsequently validated by western blotting in gastric cancer cell lines. To investigate the biological functions of PTTG1, functional assays including CCK8, colony formation, and Transwell migration and invasion assays were performed following PTTG1 knockdown in SGC-7901 and HGC-27 cells. The effects on EMT were further examined by assessing EMT-related markers by western blotting. Tumorigenic and metastatic potential in vivo was determined using a nude mouse xenograft model. The regulatory influence of PTTG1 on the TGF-β/Smad pathway was analyzed by measuring the expression levels of TGF-β, Smad2, Smad3, and their phosphorylated forms. RESULTS: PTTG1 expression was significantly upregulated in gastric cancer tissues compared with normal gastric mucosa according to TCGA data and validation in cell lines. Silencing PTTG1 in SGC-7901 and HGC-27 cells markedly inhibited proliferation and colony formation (p < 0.01), and suppressed migration and invasion (p < 0.01). Western blotting revealed increased E-cadherin and reduced N-cadherin, α-SMA, and Vimentin expression after PTTG1 knockdown. In vivo, xenograft tumor growth was significantly reduced in nude mice injected with si-PTTG1 cells compared with controls (n = 6 per group; p < 0.05). Mechanistically, PTTG1 depletion attenuated TGF-β, phosphorylated Smad2, and phosphorylated Smad3 levels, indicating inhibition of the TGF-β/Smad pathway. CONCLUSION: PTTG1 promotes gastric cancer progression by activating the TGF-β/Smad axis to enhance cell proliferation, invasion, and EMT. These findings highlight PTTG1 as a potential diagnostic biomarker and therapeutic target in gastric cancer.