PYCR1 inhibition in bone marrow stromal cells enhances bortezomib sensitivity in multiple myeloma cells by altering their metabolism.

ABSTRACT: Despite significant advancements, multiple myeloma (MM) remains incurable, largely due to drug resistance. Our previous research has demonstrated that proline metabolism plays a role in MM progression and that inhibiting PYCR1, the final enzyme in proline synthesis, enhances bortezomib sensitivity in MM cells. Given the high expression of PYCR1 in bone marrow stromal cells (BMSCs), we sought to investigate the effects of PYCR1 inhibition in BMSCs and its indirect influence on MM cell metabolism and viability. Culturing MM cells in conditioned medium (CM) of PYCR1-silenced BMSC significantly impaired oxidative phosphorylation and sensitised MM cells to bortezomib. Analysis of the CM secretome revealed a reduction in activin A release. Proline and activin A supplementation were able to count

SUBMITTER: Oudaert I 

PROVIDER: S-EPMC12936435 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature