In our model, which is schematically depicted in Fig. 4, paracrine secretion of uPA enhances MAPK signaling and ETS transcription factor activity, leading to EMT and supporting uPA expression in UCIS cells; overexpression of p16INK4a would therefore be a byproduct of this process and a candidate marker for the EMT which is occurring in the tumour cells. Here, PLAU is linked to neoplasm.