Western blot analyses show that an exogenous EGF supplementation leads to the phosphorylation, i.e., the activation of both the EGF receptor and one of its downstream target, AKT, in both shScr and shNPM1 cells. On the contrary, and most interestingly, phosphorylation of ERK1/2 is specifically impaired in shNPM1 cells. In agreement with this result, addition of exogenous EGF is unable to restore migration and invasion capacities of shNPM1 LNCaP cells in the corresponding assays. These results clearly demonstrate that NPM1 is specifically required for the activation of the MAPK signalling pathway and that the potentiation of this transduction pathway is involved in the control of proliferation and migration capacities of prostate cancer cells. NPM1 plays an essential role in cell growth and proliferation. Amongst others, it favours cell cycle progression, ribosome biogenesis and centrosome duplication. Accordingly, a correlation between increased NPM1 expression levels and tumour progression has been established in a wide set of solid tumours of diverse histological origins such as in gastric-, colon, kidney or ovary cancers. Nevertheless several studies revealed that, paradoxically, NPM1 is able to both act as a tumour suppressor and as a proto-oncogene during tumourigenesis. On one hand, NPM1 participates to the maintenance of chromosome stability and regulates ARF activity and, on the other hand, NPM1 promotes the inhibition of several tumour suppressors including P53 or Rb, and the activation of the protooncogene c-Myc to enhance its transforming activity. Our previous findings showed that the molecular chaperone NPM1 is over-expressed in prostate carcinoma tissue, compared to control adjacent tissue where it stimulates the androgen-dependent transcription. We now wanted to more specifically investigate whether this deregulation of NPM1 expression may act on prostate tumour cells invasive and migration capacities. In this regard, NPM1 was knocked-down in the LNCaP prostate cancer cell lines whose tumour characteristics such as migration, proliferation and invasion capacities are well established. We show that reducing NPM1 expression in LNCaP cells alters the clonogenic and proliferation capacities of these prostate cancer cells as well as their ability to migrate and to invade matrix-containing supports.