Abstract
Progranulin, the precursor protein to seven and a half distinct granulin motifs (GRNs), has been implicated in a broad range of diseases. Progranulin depletion is one of the most frequent causes for hereditary Frontotemporal Dementia (FTD). On the other hand, elevated progranulin levels have been associated with increased malignancy of many tumours, manifesting in increased cell proliferation, migration, metastasis formation, and reduced sensitivity to chemotherapeutics. While some functions can be unambiguously attributed to either full-length progranulin or one or multiple of the different GRNs, much about the interplay between progranulin and GRNs remains unknown. Here, we aimed to test the effect of progranulin overexpression on cell-based tumorigenicity assays, assessing proliferation, migration, and colony formation, using the hepatocellular carcinoma cell line HepG2 and the glioblastoma cell line U87. We transduced these cells with lentiviral vectors to overexpress full-length progranulin, two different C-terminally truncated progranulin proteins, lacking either the last two or the last four GRNs, or a triple FLAG-tagged maltose binding protein as a control. We observed increased colony formation in HepG2 overexpressing the full-length progranulin but not the C-terminally truncated constructs. The U87 cell lines were neither affected by an increase in progranulin levels nor by the depletion of progranulin.