{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T21:50:47Z","timestamp":1788990647171,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-25-00455"],"award-info":[{"award-number":["24-25-00455"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer is the third most common cancer worldwide, making lymph node recovery critical for treatment decisions and prognosis. Within the colorectal tumor microenvironment, the metabolic programming of tumor-associated macrophages (TAMs) can drive both pro- and anti-tumor responses, yet the specific glycolytic pathways governing their pro-metastatic conversion present promising therapeutic targets. This study investigated the role of glycolysis activating enzyme 6-phosphofructo-2-kinase\/fructose-2,6-biphosphatase 3 (PFKFB3) in mediating TAMs metabolic polarization, and its potential as a therapeutic target. PFKFB3 expression was found to be predominant in TAMs in CRC tumor samples. Lipidomic analysis performed by HPLC-MS\/MS revealed that PFKFB3 inhibition altered glycerophospholipid metabolism (p = 6.13 \u00d7 10\u221210), and shifted TAMs toward sphingolipid-mediated immunosuppressive metabolism. PFKFB3 activity was associated with a specific reduction in asparagine availability, potentially pointing to a targeted reprogramming of amino acid metabolism supporting distinct TAM functions under conditions of intra-tumoral metabolic stress. These findings highlight PFKFB3 as an essential regulator of TAMs pro-tumoral metabolism in CRC, particularly in colon cancer.<\/jats:p>","DOI":"10.3390\/ijms27010217","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T16:41:19Z","timestamp":1766594479000},"page":"217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inhibition of PFKFB3 in Macrophages Has a Dual Effect on Tumor-Regulating Lipid Metabolism"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6637-4417","authenticated-orcid":false,"given":"Elena","family":"Shmakova","sequence":"first","affiliation":[{"name":"Laboratory of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, 634050 Tomsk, Russia"},{"name":"Laboratory of Molecular Therapy of Cancer, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634014 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3835-5259","authenticated-orcid":false,"given":"Tatiana","family":"Sudarskikh","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6159-5173","authenticated-orcid":false,"given":"Kseniia","family":"Shalygina","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaliy","family":"Chagovets","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6650-5915","authenticated-orcid":false,"given":"Natalia","family":"Starodubtseva","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, 123592 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Tokareva","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Novoselova","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9780-4579","authenticated-orcid":false,"given":"Vladimir","family":"Frankevich","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"Laboratory of Translational Medicine, Siberian State Medical University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6247-3434","authenticated-orcid":false,"given":"Anna","family":"Tarasova","sequence":"additional","affiliation":[{"name":"Abdominal Department, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634014 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5691-2349","authenticated-orcid":false,"given":"Dmitry","family":"Kostromitsky","sequence":"additional","affiliation":[{"name":"Abdominal Department, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634014 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2748-0644","authenticated-orcid":false,"given":"Alexey","family":"Dobrodeev","sequence":"additional","affiliation":[{"name":"Abdominal Department, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634014 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4701-0375","authenticated-orcid":false,"given":"Sergey","family":"Afanas\u2019ev","sequence":"additional","affiliation":[{"name":"Abdominal Department, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634014 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5758-7330","authenticated-orcid":false,"given":"Irina","family":"Larionova","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, 634050 Tomsk, Russia"},{"name":"Laboratory of Molecular Therapy of Cancer, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634014 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0898-3075","authenticated-orcid":false,"given":"Julia","family":"Kzhyshkowska","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, 634050 Tomsk, Russia"},{"name":"Institute of Transfusion Medicine and Immunology, Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Riabov, V., Gudima, A., Wang, N., Mickley, A., Orekhov, A., and Kzhyshkowska, J. 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