Biochemical activity induced by a germline variation in <i>KLK3</i> (PSA) associates with cellular function and clinical outcome in prostate cancer.

ABSTRACT: Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility. The non-synonymous KLK3 SNP, rs17632542 (c.536T>C; Ile163Thr-substitution in PSA) is associated with reduced prostate cancer risk, however, the functional relevance is unknown. Here, we identify that the SNP variant-induced change in PSA biochemical activity as a previously undescribed function mediating prostate cancer pathogenesis. The 'Thr' PSA variant led to small subcutaneous tumours, supporting reduced prostate cancer risk. However, 'Thr' PSA also displayed higher metastatic potential with pronounced osteolytic activity in an experimental metastasis in-vivo model. Biochemical characterization of this PSA variant demonstrated markedly reduced proteolytic activity that correla

SUBMITTER: Srinivasan S 

PROVIDER: S-EPMC10081352 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature