Multifunctionality of prostatic acid phosphatase in prostate cancer pathogenesis

The role of human prostatic acid phosphatase (PAcP, P15309|PPAP HUMAN) in prostate cancer was investigated using a new proteomics tool termed signal sequence swapping (replacement of domains from the native cleaved amino terminal signal sequence of secretory/membrane proteins with corresponding regions of functionally distinct signal sequence subtypes). This manipulation preferentially redirects proteins to different pathways of biogenesis at the endoplasmic reticulum (ER), magnifying normally difficult to detect subsets of the protein of interest. For PAcP, this technique reveals three forms identical in amino acid sequence but profoundly different in physiological functions, subcellular location, and biochemical properties. These three forms of PAcP can also occur with the wildtype PAcP signal sequence. Clinical specimens from patients with prostate cancer demonstrate that one form, termed ^PLPAcP, correlates with early prostate cancer. These findings confirm the analytical power of this method, implicate ^PLPAcP in prostate cancer pathogenesis, and suggest novel anticancer therapeutic strategies.