WDR72 Enhances the Stemness of Lung Cancer Cells by Activating the AKT/HIF-1α Signaling Pathway.

Abstract

Lung cancer is a common malignant tumor with high morbidity and mortality rate. Lung cancer stem cells are crucial in the development of lung cancer. In this study, we investigate WD repeat-containing protein 72 (WDR72) on lung cancer cell stemness and explore its underlying mechanism. WDR72 expression was investigated in lung cancer tissues and lung cancer stem cells by Western blot and RT-qPCR. The stemness of lung cancer stem cells was verified by the sphere-forming experiment and the abundance of stem cell markers. For the purpose of determining lung cancer stem cell growth, metastasis, and apoptosis, the CCK-8 assay, colony formation, Transwell migration, and flow cytometry were carried out. The ability of tumorigenesis in vivo was explored by xenograft tumor mouse models. Up-regulation of WDR72 was found in lung cancer tissues and lung cancer stem cells. WDR72 overexpression significantly activated the AKT/HIF-1α signaling pathway. Application of PI3K/AKT pathway inhibitor LY29004 was able to counteract the impacts of WDR72 upregulation on genes related to stemness, growth, migration, and apoptosis in lung cancer stem cells. The sphere formation of lung cancer stem cells was significantly diminished after inhibiting the AKT/HIF-1α pathway. The promotion of WDR72 overexpression on lung cancer stem cell proliferation and metastasis was also eliminated by LY29004 treatment. WDR72 activates the AKT/HIF-1α signaling pathway to enhance the stemness of lung cancer stem cells and promote the growth and metastasis of lung cancer.