PFKFB3 promotes proliferation, migration and angiogenesis in nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is a squamous epithelial cancer, arising from the nasopharynx epithelium. It has high morbidity and mortality. PFKFB3 as a glycolytic activator has been implicated in the progression of multiple types of tumor. PFKFB3 can be contributed to the progression and metastasis of cancer. However, whether PFKFB3 is associated with the progression of NPC remains unknown. We postulated that PFKFB3 promotes proliferation, migration and angiogenesis in nasopharyngeal carcinoma. In this study, we found that PFKFB3 was significantly up-regulated in NPC tissues and cell lines compared with normal control. Our study proved that PFKFB3 can regulate the proliferation, metastasis and apoptosis of NPC. By the way, the NPC-derived exosomes come from and CNE2-derived exosomes are enriched in PFKFB3. The enrichment of PFKFB3 played a crucial functional role in promotes HUVECs proliferation, migration and angiogenesis. And tumor angiogenesis is closely related to the proliferation and metastasis of tumor. In conclusion, our findings demonstrate that PFKFB3 could act not only as a clinical biomarker for angiogenesis but also as a therapeutic target to overcome angiogenesis, enhancing the clinical benefits of angiogenesis therapy in NPC patients.

PFKFB4 Promotes Breast Cancer Metastasis via Induction of Hyaluronan Production in a p38-Dependent Manner

“…In addition, PFKFB3 plays a role in tumor metastasis in head and neck squamous cell carcinoma and nasopharyngeal carcinoma [36,37]. Previous reports indicate that HA accumulation occurs in numerous tumor types and thereby facilitates the progression and metastasis of carcinomas [38,39].…”

Extracellular Vesicle Membrane-Associated Proteins: Emerging Roles in Tumor Angiogenesis and Anti-Angiogenesis Therapy Resistance

“…This uptake can occur through clathrin-dependent endocytosis and/or clathrin-independent pathways such as caveolin-mediated endocytosis, macropinocytosis, phagocytosis, and lipid raft-mediated internalization [6,7]. EVs have been found to encapsulate various luminal cargo with angiogenic properties, and the activity of these constituents is contingent upon EV uptake by recipient cells [9][10][11][12][13]. However, increasing evidence indicates that the surfaces of EVs display a repertoire of membrane-bound proteins that stimulate various steps in the angiogenic cascade, and may do so independently of EV uptake.…”

“…To date, the biological responses induced by EVs in the tumor microenvironment and in other contexts have been largely thought to be mediated through the transfer of their luminal cargo into recipient cells. A number of studies have shown that cancer cell-derived EVs stimulate endothelial cell survival, migration and tube formation in vitro and tumor angiogenesis in vivo, and have attributed these responses to various luminal constituents, such as enzymes and non-coding RNAs, that are encapsulated in EVs and transferred into endothelial cells [9][10][11][12][13]. However, recent studies have revealed that the EV membrane is not solely composed of structural components but displays a rich array of biologically active proteins with angiogenic properties.…”

Functional Analysis of O-GlcNAcylation in Cancer Metastasis

“…Decreasing O-GlcNAcylation of this protein via OGT inhibition or knockdown in breast cancer cells increases both SIRT1 level and activity, thereby regulating forkhead box M1 (FOXM1), MMP-2, and MMP-9 protein level, and modulating breast cancer cell invasive and metastatic capability in vitro and in vivo (42). Via MMP targeting, O-GlcNAcylation plays an important role in cancer metastasis (47,95,100,101,(106)(107)(108)(109)(110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121).…”

“…As a typical example (17,(122)(123)(124)(125)(126)(127), both O-GlcNAcylation and phosphorylation occur on Ser/Thr residues of substrate proteins, and extensive crosstalk between two PTMs through mutual inhibition of the same or nearby residues has been identified (108). 6-phosphofructo-2-kinase/fructose-2,6bisphosphatase 3 (PFKFB3), a glycolytic regulator, can be O-GlcNAcylated and phosphorylated at Ser172, and the competition between these two PTMs regulates the function of PFKFB3 in promoting nasopharyngeal carcinoma and gastric cancer proliferation, as well as migration (109)(110)(111). The enhancer of zeste homolog (EZH2) is responsible for H3K27me3, which promotes the metastasis of cancers such as melanoma and breast cancer (112,113).…”