Progranulin Oncogenic Network in Solid Tumors

Abstract

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.

Glioblastoma biomarkers in urinary extracellular vesicles reveal the potential for a ‘liquid gold’ biopsy

“…GRN is a pleiotropic growth factor with important roles in several physiological processes; GRN deficiency is associated with a broad range of pathological conditions affecting the brain, such as frontotemporal dementia. GRN is upregulated in neoplastic tissues, and has a pro-tumorigenic role by promoting cancer cell proliferation, migration, invasiveness, anchorage-independent growth, modulation of the tumour microenvironment, immune evasion and resistance to chemotherapy [ 57 ]. GRN is a known glioma-associated growth factor [ 58 ], its overexpression in GBM tumours and prognostic significance is well established [ 59 ].…”

Relationship of progranulin response with some physio-biochemical parameters in Akkaraman sheep

“…PGRN is an adipokine that plays a key role in many physiological and pathological processes, such as autocrine growth factor, inflammation, glucose and lipid metabolism, as well as its regulating effect on insulin resistance (Liu, 2011;Matsubara et al, 2012;Sun et al, 2022;Ventura et al, 2023). PGRN, a growth factor, has a role in mammary gland development in lactation, embryogenesis during pregnancy, preservation of cervical tissue, and fetal growth (He and Baterman,2003;Desmarais et al, 2008;Andres and Djonov, 2010;Stubert et al, 2012).…”

Progranulin and GPNMB: interactions in endo-lysosome function and inflammation in neurodegenerative disease

“…Toxicity from increased PGRN is the primary concern. While necessary for endo-lysosomal health during aging, PGRN in excess could become toxic and contribute to hyperplasia of certain tissues [218][219][220][221]. Furthermore, the AAV vectors must also be tolerated by patients' immune systems.…”