{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T01:22:51Z","timestamp":1787102571130,"version":"build-2736575974"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Glycolysis has been reported to be critical for cancer stem cells (CSCs), which are associated with tumor chemoresistance, metastasis and recurrence. Thus, selectively targeting glycolytic enzymes may be a potential therapy for ovarian cancer. 6\u2010phosphofructo\u20102\u2010kinase\/fructose\u20102,6\u2010biphosphatase 3 (PFKFB3), the main source of fructose-2,6-bisphosphate, controls the first committed step in glycolysis. We investigate the clinical significance and roles of PFKFB3 in ovarian cancer using <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experiments. We demonstrate that PFKFB3 is widely overexpressed in ovarian cancer and correlates with advanced stage\/grade and poor outcomes. Significant up-regulation of PFKFB3 was found in ascites and metastatic foci, as well as CSC-enriched tumorspheres and ALDH+CD44+ cells. 3PO, a PFKFB3 inhibitor, reduced lactate level and sensitized A2780CP cells to cisplatin treatment, along with the modulation of inhibitors of apoptosis proteins (c-IAP1, c-IAP2 and survivin) and an immune modulator CD70. Blockade of PFKFB3 by siRNA approach in the CSC-enriched subset led to decreases in glycolysis and CSC properties, and activation of the NF-\u03baB cascade. PFK158, another potent inhibitor of PFKFB3, impaired the stemness of ALDH+CD44+ cells <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, whereas ectopic expression of PFKFB3 had the opposite results. Overall, PFKFB3 was found to mediate metabolic reprogramming, chemoresistance, metastasis and stemness in ovarian cancer, possibly <jats:italic>via<\/jats:italic> the modulation of inhibitors of apoptosis proteins and the NF-\u03baB signaling pathway; thus, suggesting that PFKFB3 may be a potential therapeutic target for ovarian cancer.<\/jats:p>","DOI":"10.3389\/fonc.2022.748403","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T10:06:21Z","timestamp":1643364381000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["PFKFB3 Regulates Chemoresistance, Metastasis and Stemness via IAP Proteins and the NF-\u03baB Signaling Pathway in Ovarian Cancer"],"prefix":"10.3389","volume":"12","author":[{"given":"Yu-xin","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle K. 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