Cereblon (CRBN) inhibits prostate cancer cell migration and invasion by regulating 6-Phosphogluconate dehydrogenase (6PGD)

Abstract

As the third enzyme of the pentose phosphate pathway (PPP), 6-phosphogluconate dehydrogenase (6PGD) has been reported to be abnormally high in many human cancers. I report that the underlying mechanism of elevated 6PGD expression in metastatic prostate cancer cells is caused by low cereblon (CRBN) protein expression. By confirming that 6PGD interacts directly with CRBN and is ubiquitinated by the CRL4CRBN, I establish 6PGD as a new endogenous substrate for CRBN. Furthermore, CRBN negatively regulates prostate cancer cell progression and metastasis as aberrantly elevated 6PGD—in the absence of sufficient CRBN—increases metastatic potential in prostate cancer in vitro and in vivo. This study provides compelling evidence that carbohydrate metabolism mediated by 6PGD is linked to prostate cancer metastasis through CRBN. From these findings, I propose that the 6PGD-CRBN axis may be a promising target for further research into new treatments for mitigating prostate cancer metastasis