POU5F1 promotes the proliferation, migration, and invasion of gastric cancer cells by reducing the ubiquitination level of TRAF6

POU5F1 plays an important role in maintaining the cancer stem cell (CSC) -like properties of gastric cancer (GC) cells. The impact of POU5F1 on the proliferation and metastasis of GC was examined, along with the potential of ATRA as a specific therapeutic agent for GC. The dysregulation of POU5F1 expression in GC tissues was analyzed using public databases and bioinformatics techniques, and the disparity in POU5F1 expression between normal gastric tissues and GC tissues was further assessed through western blot, RT-qPCR, and immunohistochemistry. The present study aimed to investigate the impact of POU5F1 on the proliferation, migration, and invasion of GC cells through both in vivo and in vitro experiments. Additionally, the effects of ATRA on the proliferation, migration, and invasion of GC cells were examined using in vivo and in vitro approaches. Our findings revealed a significant upregulation of POU5F1 in GC tissues, which was found to be associated with a poorer prognosis in patients with GC. Moreover, POU5F1 was observed to enhance the proliferation, migration, and invasion of GC cells in vitro, as well as promote subcutaneous tumor growth and lung metastasis of GC cells in vivo. The overexpression of POU5F1 mechanistically triggers the process of Epithelial-mesenchymal transition (EMT) by down-regulating E-Cadherin and up-regulating N-Cadherin and VIM. POU5F1 hinders the ubiquitination of TRAF6 through negative regulation of TRIM59, thereby facilitating the activation of the NF-kappa B pathway. Furthermore, the administration of ATRA effectively impedes the proliferation, migration, and invasion of GC cells by suppressing the expression of POU5F1. The upregulation of POU5F1 elicits EMT, fosters the initiation of the NF-kappa B signaling pathway in GC cells, and stimulates the proliferation, invasion, and metastasis of GC cells. All-trans retinoic acid (ATRA) can impede these POU5F1-induced effects, thereby potentially serving as an adjunctive therapeutic approach for GC.

Automated summary

POU5F1 plays a crucial role in maintaining cancer stem cell-like properties in gastric cancer cells. Overexpression of POU5F1 is associated with a poor prognosis in gastric cancer patients. POU5F1 enhances the proliferation, migration, and invasion of gastric cancer cells by triggering Epithelial-mesenchymal transition (EMT) and activating the NF-kappa B pathway. ATRA, a therapeutic agent, inhibits the expression of POU5F1 and effectively impedes the proliferation, migration, and invasion of gastric cancer cells.