A Potential Oncogenic Role for PFKFB3 Overexpression in Gastric Cancer Progression. Issue 7 (1st July 2021)

• Record Type: Journal Article
• Authors: Lei, Lan; Hong, Lian-Lian; Ling, Zhe-Nan; Zhong, Yi; Hu, Xuan-Yu; Li, Pei; Ling, Zhi-Qiang
• Is Part Of: Clinical and translational gastroenterology. Volume 12:Issue 7(2021)
• Page Start: e00377
• Publication Date: 2021-07-01
• Subjects: Stomach -- Diseases -- Periodicals; Intestines -- Diseases -- Periodicals; Gastroenterology; Gastrointestinal Diseases; Liver Diseases; Intestines -- Diseases; Stomach -- Diseases; Periodical; Periodicals; Fulltext; Internet Resources; Periodicals; Electronic journals; 616.33
• DOI: 10.14309/ctg.0000000000000377
• Languages: English
• ISSNs: 2155-384X

Abstract

Abstract : OBJECTIVES: PFKFB3 regulates glycolysis in tumor cells, might function as an oncogene, and is associated with cancer metastasis. However, its role in gastric cancer (GC) remains largely unknown. METHODS: PFKFB3 expression was assessed by immunohistochemistry (IHC) in GC tissues and paired paracancerous histological normal tissues (PCHNTs). The associations of PFKFB3 expression with clinical features and HIF-1α, Ki-67, E-cadherin, Snail, and Vimentin expression levels were assessed. A series of in vivo and in vitro experiments were performed to investigate the effects of PFKFB3 on the growth, migration, and invasion of GC cells. RESULTS: We found that PFKFB3 expression was significantly higher in GC tissues compared with PCHNTs ( P = 0.000). PFKFB3 expression was positively correlated with tumor size ( P = 0.000), differentiation ( P = 0.025), venous invasion ( P = 0.084), nerve invasion ( P = 0.014), lymphatic invasion ( P = 0.000), local invasion ( P = 0.000), invasive depth ( P = 0.000), nodal metastasis ( P = 0.000), tumor-node-metastasis stage ( P = 0.000), and patient survival ( P = 0.000). Notably, PFKFB3 upregulation was highly correlated with increased epithelial-mesenchymal transition (EMT) in GC samples. PFKFB3 overexpression positively modulated cell proliferation, migration, and EMT in GC cells in vitro, with concomitant activation of NF-κB signaling. Administration of an NF-κB inhibitor attenuated PFKFB3-induced EMT in GC cells. PFKFB3 overexpression promoted tumor development and EMT in nude mice, which were attenuated by PFK-15, a PFKFB3 inhibitor. DISCUSSION: PFKFB3 could potentiate malignancy in GC cells through NF-κB pathway–mediated EMT, suggesting PFKFB3 represents a potential target for GC therapy.