{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:02:18Z","timestamp":1789718538141,"version":"4.0.1"},"reference-count":145,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"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. Cell Dev. Biol."],"abstract":"<jats:p>Metabolic reprogramming is a hallmark of malignant tumors. Platelet-type phosphofructokinase (PFKP), a rate-limiting enzyme in glycolysis, is aberrantly overexpressed across diverse cancers and promotes tumor proliferation, invasion, and metastasis through both metabolic and non-metabolic pathways. The enzymatic activity, stability, and subcellular localization of PFKP are dynamically regulated by post-translational modifications\u2014including phosphorylation, ubiquitination, acetylation, and lactylation\u2014as well as by protein\u2013protein interaction networks. Upon nuclear translocation, PFKP dissociates from glycolytic flux and engages in oncogenic transcriptional regulation. Moreover, PFKP upregulates PD-L1 expression, alters chemokine profiles, disrupts immune cell infiltration, and fosters an immunosuppressive microenvironment that facilitates immune evasion. Emerging evidence suggests PFKP holds diagnostic and prognostic potential, yet direct targeting evidence remains lacking, and most inhibitor studies are confined to preclinical models. This review synthesizes recent advances in PFKP research, focusing on its regulatory networks in tumor metabolism, post-translational modifications, protein interactions, and immune remodeling. We critically evaluate current controversies, unresolved questions, and translational barriers, and propose future directions\u2014including epigenetic regulation, functional characterization of interacting partners, and combination strategies with immunotherapy\u2014to inform precision oncology and targeted therapeutic development.<\/jats:p>","DOI":"10.3389\/fcell.2026.1944968","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:11:50Z","timestamp":1789715510000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PFKP in malignant tumors: bridging metabolic reprogramming, post-translational modifications, and the immunosuppressive microenvironment"],"prefix":"10.3389","volume":"14","author":[{"given":"Jing-Jing","family":"Zhao","sequence":"first","affiliation":[{"name":"Chinese Medicine Guangdong Laboratory\/State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangyuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Chinese Medicine Guangdong Laboratory\/State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)","place":["Guangzhou, Guangdong, China"]},{"name":"Guangzhou Laboratory","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zong","sequence":"additional","affiliation":[{"name":"Chinese Medicine Guangdong Laboratory\/State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Chinese Medicine Guangdong Laboratory\/State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yicheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Chinese Medicine Guangdong Laboratory\/State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Liu","sequence":"additional","affiliation":[{"name":"Chinese Medicine Guangdong Laboratory\/State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runze","family":"Li","sequence":"additional","affiliation":[{"name":"Chinese Medicine Guangdong Laboratory\/State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1101\/2022.08.02.22277946","article-title":"Gene expression levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence and risk of death in cervical","author":"Bola\u00f1os-Su\u00e1rez","year":"2022","journal-title":"Cancer"},{"key":"B2","doi-asserted-by":"publisher","first-page":"15632","DOI":"10.1002\/cam4.6123","article-title":"The mRNA and protein levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence, and risk of death in cervical cancer patients","volume":"12","author":"Bolanos-Suarez","year":"2023","journal-title":"Cancer Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e151295","DOI":"10.1172\/jci151295","article-title":"All in for nuclear PFKP-induced CXCR4 metastasis: a T cell acute lymphoblastic leukemia prognostic marker","volume":"131","author":"Broxmeyer","year":"2021","journal-title":"J. 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