2. Academic Validation
  3. AKR1B10 negatively regulates autophagy through reducing GAPDH upon glucose starvation in colon cancer

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

  • J Cell Sci. 2021 Apr 15;134(8):jcs255273. doi: 10.1242/jcs.255273.
Wanyun Li 1,  Cong Liu 1,  Zilan Huang 1,  Lei Shi 1,  Chuanqi Zhong 2,  Wenwen Zhou 1,  Peipei Meng 1,  Zhenyu Li 1,  Shengyu Wang 1,  Fanghong Luo 1,  Jianghua Yan 1,  Ting Wu 1 3 4 5
Affiliations

Affiliations

  • 1 Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361000, China.
  • 2 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cellular Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361000, China.
  • 3 Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen 361000, China.
  • 4 Xiamen University Research Center of Retroperitoneal Tumor Committee of Oncology Society of Chinese Medical Association, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361000, China.
  • 5 Joint Laboratory of Xiamen University School of Medicine and Shanghai Jiangxia Blood Technology Co., Ltd., Xiamen 361000, China.
PMID: 33758077 DOI: 10.1242/jcs.255273
Abstract

Autophagy is considered to be an important switch for facilitating normal to malignant cell transformation during colorectal Cancer development. Consistent with other reports, we found that 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 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 importation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and then subsequently represses Autophagy. Interestingly, we also found that an NADPH-dependent reduction reaction could be induced when AKR1B10 interacts with GAPDH, and the reductase activity of AKR1B10 is important for its repression of Autophagy. Together, our findings unravel a novel mechanism of NRP1 in regulating Autophagy through AKR1B10.

Keywords

Aldo-keto reductase family 1 B10, AKR1B10; Glucose starvation; Glyceraldehyde-3-phosphate dehydrogenase, GAPDH; Neuropilin1, NRP1; Nuclear translocation; Reductase activity.

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