Intriguingly, in the TRAMP model of PCa (a genetic model that expresses the SV40 T antigen in the prostate), crossing with the systemic knockout OPN model resulted in more aggressive prostate cancer characterized by increased tumor mass, reduced survival, greater dedifferentiation, and a shift towards a neuroendocrine phenotype, which was linked to the downregulation of the TGF-β pathway [136]. This evidence concerns the gene SPP1 and prostate cancer.