Cereblon (CRBN) inhibits prostate cancer metastasis by negatively regulating 6-phosphogluconate dehydrogenase (6PGD) - PubMed
2 days ago
- #CRBN-6PGD axis
- #metastasis
- #prostate cancer
- Cereblon (CRBN) inhibits prostate cancer metastasis by negatively regulating 6-phosphogluconate dehydrogenase (6PGD).
- CRBN promotes polyubiquitination and proteasomal degradation of 6PGD, a key enzyme in the oxidative pentose phosphate pathway (oxPPP).
- Loss of CRBN stabilizes 6PGD, increasing the NADPH/NADP+ ratio and enhancing cancer cell migration and invasion.
- Re-expression of CRBN reduces 6PGD levels, restores NADPH/NADP+ balance, and suppresses metastasis.
- Transcriptomic analysis shows CRBN upregulates CDH1 and downregulates EMT marker MMP1, effects reversed by 6PGD inhibition.
- CRBN's tumor-suppressive role is conserved across cancer cell lines and in CRBN-deficient mouse tissues.
- Intra-splenic xenograft models confirm CRBN's role in suppressing metastatic dissemination.
- The CRBN-6PGD axis is identified as a critical metabolic checkpoint in prostate cancer metastasis.