AKR1B10 negatively regulates autophagy through reducing GAPDH upon glucose starvation in colon cancer.

Autophagy is considered as an important switch for cell transformation from normal to malignant during colorectal cancer development. Consistent with other reports, we found the membrane receptor Neuropilin1 (NRP1) is greatly upregulated in colon cancer cells that underwent autophagy upon glucose deprivation. However, the mechanism underlying NRP1 regulation of autophagy is unknown. We found that knockdown of the NRP1 inhibits autophagy and largely upregulates the expression of Aldo-Keto Reductase family 1 B10 (AKR1B10). Moreover, we demonstrated that AKR1B10 interacts with and inhibits the nuclear import of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and then subsequently represses autophagy. Interestingly, we also found a NADPH-dependent reduction reaction could be induced when AKR1B10 interacts with GAPDH and the reductase activity of AKR1B10 is important for its repressing autophagy. Together, our findings unravel a novel mechanism of NRP1 in regulating autophagy through AKR1B10.