Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 6, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2018.00066
Keywords
collagen; extracellular matrix; lysyl hydroxylation; procollagen-lysine 2-oxoglutarate 5-dioxygenase; cancer progression
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Funding
- NCI [1R01CA207772, 1R01CA215095, 1R21CA209045]
- United States Department of Defense [W81XWH-15-1-0052]
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Collagen is the major component of extracellular matrix. Collagen cross-link and deposition depend on lysyl hydroxylation, which is catalyzed by procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD). Aberrant lysyl hydroxylation and collagen cross-link contributes to the progression of many collagen-related diseases, such as fibrosis and cancer. Three lysyl hydroxylases (LH1, LH2, and LH3) are identified, encoded by PLOD1, PLOD2, and PLOD3 genes. Expression of PLODs is regulated by multiple cytokines, transcription factors and microRNAs. Dysregulation of PLODs promotes cancer progression and metastasis, suggesting that targeting PLODs is potential strategy for cancer treatment. Here, we summarize the recent progress in the investigation of function and regulation of PLODs in normal tissue development and disease progression, especially in cancer.
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