Multifunctionality of prostatic acid phosphatase in prostate cancer pathogenesis

Abstract

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.

Metastatic Castration-Resistant Prostate Cancer: Insights on Current Therapy and Promising Experimental Drugs

“…The prostatic acid phosphatase (PAP) is a glycoprotein with enzymatic activity whose levels increase in advanced PC. 57 Sipuleucel-T is an autologous cancer "vaccine". 58,59 To prepare Sipuleucel, the white blood cell fraction containing antigen-presenting cells from each patient is collected.…”

Cytotoxic Activity of α-Aminophosphonic Derivatives Coming from the Tandem Kabachnik–Fields Reaction and Acylation

“…Prostatic acid phosphatase (PAP) originates in the prostate and is normally present in small amounts in the blood. Elevated levels of PAP in patients indicate the progression of various tumors such as prostate cancer [55], testicular cancer, leukemia, etc. Various α-benzylaminobenzylphosphonic acid derivatives have been developed over the years using structure-based drug design methods that led to the identification of low nanomolar inhibitors [56].…”