{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:19:21Z","timestamp":1792214361591,"version":"4.4.0"},"reference-count":172,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sbarro Health Research Organization"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Progranulin is a pleiotropic growth factor with important physiological roles in embryogenesis and maintenance of adult tissue homeostasis. While-progranulin deficiency is associated with a broad range of pathological conditions affecting the brain, such as frontotemporal dementia and neuronal ceroid lipofuscinosis, progranulin upregulation characterizes many tumors, including brain tumors, multiple myeloma, leiomyosarcoma, mesothelioma and epithelial cancers such as ovarian, liver, breast, bladder, adrenal, prostate and kidney carcinomas. The increase of progranulin levels in tumors might have diagnostic and prognostic significance. In cancer, progranulin has a pro-tumorigenic role by promoting cancer cell proliferation, migration, invasiveness, anchorage-independent growth and resistance to chemotherapy. In addition, progranulin regulates the tumor microenvironment, affects the function of cancer-associated fibroblasts, and modulates tumor immune surveillance. However, the molecular mechanisms of progranulin oncogenic function are not fully elucidated. In bladder cancer, progranulin action relies on the activation of its functional signaling receptor EphA2. Notably, more recent data suggest that progranulin can also modulate a functional crosstalk between multiple receptor-tyrosine kinases, demonstrating a more complex and context-dependent role of progranulin in cancer. Here, we will review what is currently known about the function of progranulin in tumors, with a focus on its molecular mechanisms of action and regulation.<\/jats:p>","DOI":"10.3390\/cancers15061706","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T03:03:57Z","timestamp":1678676637000},"page":"1706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Progranulin Oncogenic Network in Solid Tumors"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5999-7613","authenticated-orcid":false,"given":"Elisa","family":"Ventura","sequence":"first","affiliation":[{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-7471","authenticated-orcid":false,"given":"Giacomo","family":"Ducci","sequence":"additional","affiliation":[{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"},{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy"},{"name":"SYSBIO (Centre of Systems Biology), ISBE (Infrastructure Systems Biology Europe), 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reyes","family":"Benot Dominguez","sequence":"additional","affiliation":[{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3497-671X","authenticated-orcid":false,"given":"Valentina","family":"Ruggiero","sequence":"additional","affiliation":[{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"},{"name":"Department of Pharmacological Sciences, Master Program in Pharmaceutical Biotechnologies, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6181-4193","authenticated-orcid":false,"given":"Antonino","family":"Belfiore","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Endocrinology Unit, University of Catania, Garibaldi-Nesima Hospital, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3190-7671","authenticated-orcid":false,"given":"Elena","family":"Sacco","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy"},{"name":"SYSBIO (Centre of Systems Biology), ISBE (Infrastructure Systems Biology Europe), 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8690-2587","authenticated-orcid":false,"given":"Marco","family":"Vanoni","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy"},{"name":"SYSBIO (Centre of Systems Biology), ISBE (Infrastructure Systems Biology Europe), 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5908-5112","authenticated-orcid":false,"given":"Renato V.","family":"Iozzo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Anatomy and Cell Biology, Translational Cellular Oncology Program, Sidney Kimmel Cancer Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5959-016X","authenticated-orcid":false,"given":"Antonio","family":"Giordano","sequence":"additional","affiliation":[{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"},{"name":"Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2319-7884","authenticated-orcid":false,"given":"Andrea","family":"Morrione","sequence":"additional","affiliation":[{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1006\/dbio.1999.9564","article-title":"Modulation of mouse preimplantation embryo development by acrogranin (epithelin\/granulin precursor)","volume":"217","author":"Stein","year":"2000","journal-title":"Dev. 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