Authors
Philipp N Becker, Vera A Kulow, Claudia S Czopek, Kameliya Roegner, Gohar Ter-Avetisyan, Anica Loth, Bianca Nitzsche, Cem Erdogan, Adrian Schreiber, Michael Höpfner, Michael Fähling, Robert Labes
Published in
Cells. Volume 15. Issue 7. Mar 31, 2026. Epub Mar 31, 2026.
Abstract
Clear cell renal cell carcinoma (ccRCC) is characterized by profound metabolic reprogramming and limited responsiveness to therapeutic stressors, including epigenetic modulation. How glycolytic enzymes contribute to metabolic stress tolerance in ccRCC remains incompletely understood. We investigated the role of the glycolytic enzyme 2,3-bisphosphoglycerate mutase (BPGM) using human tumor specimens, siRNA-mediated gene silencing, functional cell-based assays, and transcriptomic profiling. Epigenetic stress was induced using Vorinostat as a pan-histone deacetylase inhibitor. BPGM expression was consistently elevated in human ccRCC compared with adjacent normal kidney tissue. A498 cells exhibited high basal BPGM levels and limited sensitivity to Vorinostat, whereas BPGM depletion increased cellular stress responses and reduced proliferative capacity. Despite similar phenotypic outcomes, BPGM silencing and Vorinostat treatment triggered distinct transcriptional programs. While HDAC inhibition induced widespread transcriptional changes, BPGM loss elicited a focused stress-associated response, consistent with activation of the unfolded protein response, increased lipid peroxidation, and induction of ER stress-associated genes. Our data identify BPGM as a metabolic player contributing to stress-adaptive transcriptional states in ccRCC and suggest that targeting metabolic stress adaptation may complement epigenetic strategies in renal cancer.
PMID:
41972721
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.
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