Prolyl Carboxypeptidase Maintains Receptor Tyrosine Kinase Signaling and Is a Potential Therapeutic Target in Triple Negative Breast Cancer.

ABSTRACT: TNBC is an aggressive cancer sub-type with limited treatment options and poor prognosis. New therapeutic targets are needed to improve outcomes in TNBC patients. PRCP is a lysosomal serine protease that cleaves peptide substrates when the penultimate amino acid is proline. A role for PRCP in TNBC or other cancers, and its potential as a therapy target has not yet been tested. In the current study, we found high tumor expression of PRCP associates with worse outcome and earlier recurrence in TNBC patients. Knockdown of PRCP or treatment with a small molecule PRCP inhibitor blocked proliferation and survival in TNBC cell lines and inhibited growth of TNBC tumors in mice. Mechanistically, we found PRCP maintains signaling from multiple receptor tyrosine kinases (RTKs), potentially by promotin

SUBMITTER: Duan L 

PROVIDER: S-EPMC8833515 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature