Multifunctionality of prostatic acid phosphatase in prostate cancer pathogenesis

• Published in: Bioscience reports Vol. 41; no. 10; p. 1
• Main Authors: Alpert, Evgenia, Akhavan, Armin, Gruzman, Arie, Hansen, William J, Lehrer-Graiwer, Joshua, Hall, Steven C, Johansen, Eric, McAllister, Sean, Gulati, Mittul, Lin, Ming-Fong, Lingappa, Vishwanath R
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd The Biochemical Society 29.10.2021; Portland Press Ltd
• Subjects: Acid phosphatase; Acid Phosphatase - genetics; Acid Phosphatase - metabolism; Amino acid sequence; Amino acids; Androgens; Androgens - pharmacology; Antineoplastic Agents, Hormonal - pharmacology; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biosynthesis; Cancer; Cell Cycle, Growth & Proliferation; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Diagnostics & Biomarkers; Drug Resistance, Neoplasm; Early Detection of Cancer; Endocrinology; Endoplasmic reticulum; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - enzymology; Endoplasmic Reticulum - genetics; Endoplasmic Reticulum - pathology; Humans; Hypotheses; Isoenzymes; Male; Membrane proteins; Molecular Bases of Health & Disease; Pathogenesis; Phosphatase; Predictive Value of Tests; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Protein Conformation; Proteins; Proteomics; Structure-Activity Relationship; prostate cancer; human prostatic acid phosphatase; androgen sensitivity; signal sequence
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20211646

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.