Progranulin Oncogenic Network in Solid Tumors
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 ceroi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/6/1706 |
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| author | Elisa Ventura Giacomo Ducci Reyes Benot Dominguez Valentina Ruggiero Antonino Belfiore Elena Sacco Marco Vanoni Renato V. Iozzo Antonio Giordano Andrea Morrione |
| author_facet | Elisa Ventura Giacomo Ducci Reyes Benot Dominguez Valentina Ruggiero Antonino Belfiore Elena Sacco Marco Vanoni Renato V. Iozzo Antonio Giordano Andrea Morrione |
| author_sort | Elisa Ventura |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T06:49:14Z |
| format | Article |
| id | doaj.art-0b3fcf7f3c184db485c767df05a7384f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T06:49:14Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0b3fcf7f3c184db485c767df05a7384f2023-11-17T10:06:04ZengMDPI AGCancers2072-66942023-03-01156170610.3390/cancers15061706Progranulin Oncogenic Network in Solid TumorsElisa Ventura0Giacomo Ducci1Reyes Benot Dominguez2Valentina Ruggiero3Antonino Belfiore4Elena Sacco5Marco Vanoni6Renato V. Iozzo7Antonio Giordano8Andrea Morrione9Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USASbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USASbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USASbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USADepartment of Clinical and Experimental Medicine, Endocrinology Unit, University of Catania, Garibaldi-Nesima Hospital, 95122 Catania, ItalyDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, ItalyDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, ItalyDepartment 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, USASbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USASbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USAProgranulin 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.https://www.mdpi.com/2072-6694/15/6/1706progranulinsolid tumorsRTKs |
| spellingShingle | Elisa Ventura Giacomo Ducci Reyes Benot Dominguez Valentina Ruggiero Antonino Belfiore Elena Sacco Marco Vanoni Renato V. Iozzo Antonio Giordano Andrea Morrione Progranulin Oncogenic Network in Solid Tumors Cancers progranulin solid tumors RTKs |
| title | Progranulin Oncogenic Network in Solid Tumors |
| title_full | Progranulin Oncogenic Network in Solid Tumors |
| title_fullStr | Progranulin Oncogenic Network in Solid Tumors |
| title_full_unstemmed | Progranulin Oncogenic Network in Solid Tumors |
| title_short | Progranulin Oncogenic Network in Solid Tumors |
| title_sort | progranulin oncogenic network in solid tumors |
| topic | progranulin solid tumors RTKs |
| url | https://www.mdpi.com/2072-6694/15/6/1706 |
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