Abstract
L-proline catabolism is emerging as a key pathway that is critical to cellular metabolism, growth, survival, and death. Proline dehydrogenase (PRODH) enzyme, which catalyzes the first step of proline catabolism, has diverse functional roles in regulating many pathophysiological processes, including apoptosis, autophagy, cell senescence, and cancer metastasis. Notably, accumulated evidence demonstrated that PRODH plays complex role in many types of cancers. In this review, we briefly introduce the function of PRODH, then its expression in different types of cancer. We next discuss the regulation of PRODH in cancer, the downstream pathways of PRODH and the therapies that are under investigation. Finally, we propose novel insights for future perspectives on the modulation of PRODH.
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Abbreviations
- PRODH:
-
Proline dehydrogenase
- POX:
-
Proline oxidase
- EAAs:
-
Essential amino acids
- NEAAs:
-
Non-essential amino acids
- TNBC:
-
Triple-negative breast cancer
- P5C:
-
Pyrroline-5-carboxylate
- ETC:
-
Electron transport chain
- TCA:
-
Tricarboxylic acid cycle
- PYCRS:
-
P5C reductase
- PIG6:
-
P53-induced gene-6
- PPARγ:
-
Peroxisome proliferator activated receptor gamma
- TZDs:
-
Thiazolidinediones
- oxLDL:
-
Oxidized low-density lipoprotein
- TME:
-
Tumor microenvironment
- CSC:
-
Cancer stem cell
- EMT:
-
Epithelial–mesenchymal transition
- NSCLC:
-
Non-small cell lung cancer
- PDAC:
-
Pancreatic ductal adenocarcinoma
- PCa:
-
Prostate cancer
- BRCA:
-
Breast invasive carcinoma
- LUAD:
-
Lung adenocarcinoma
- MMBC:
-
Multifocal/multicentric breast cancer
- UFBC:
-
Unifocal breast cancer
- NFAT:
-
Nuclear factor of activated T cells
- TRAIL:
-
Tumor necrosis factor-related apoptosis inducing ligand
- NAC:
-
N-acetyl-L-cysteine
- L-THFA:
-
L-tetrahydro-2-furoic acid
- AICAR:
-
5-Aminoimidazole-4-carboxamide ribonucleoside
- NF-κB:
-
Nuclear factor κB
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This work is supported by National Natural Science Foundation of China [82002916 (CM), 81874139 and 82073097 [SL], 81872285[YS], 82072594 [YT], 82073136 [DX]], Natural Science Foundation of Hunan Province [2020JJ5790 (CM)], China Postdoctoral Science Foundation [2019M652804 (CM)] and Postdoctoral Foundation of Central South University [220372 (CM)], Shenzhen Science and Technology Program (KQTD20170810160226082 [YT]), Shenzhen Municipal Government of China (JCYJ20180507184647104 [YT]), and the Hunan Provincial Key Area R&D Program (2019SK2253[YT]).
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Liu, Y., Mao, C., Liu, S. et al. Proline dehydrogenase in cancer: apoptosis, autophagy, nutrient dependency and cancer therapy. Amino Acids 53, 1891–1902 (2021). https://doi.org/10.1007/s00726-021-03032-5
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DOI: https://doi.org/10.1007/s00726-021-03032-5