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Updated: Jul 6, 2026

Evaluation of Amino Acid Consumption in Cultured Bone Cells and Isolated Bone Shafts
Published on: April 13, 2022
The metabolism of proline, a stress substrate, modulates carcinogenic pathways
James M Phang1, Steven P Donald, Jui Pandhare
1Laboratory of Comparative Carcinogenesis, Center for Cancer Research, Building 538, Room 115, NCI-Frederick, Frederick, MD 21702, USA. phang@mail.ncifcrf.gov
Abstract:
The resurgence of interest in tumor metabolism has led investigators to emphasize the metabolism of proline as a "stress substrate" and to suggest this pathway as a potential anti-tumor target. Proline oxidase, a.k.a. proline dehydrogenase (POX/PRODH), catalyzes the first step in proline degradation and uses proline to generate ATP for survival or reactive oxygen species for programmed cell death. POX/PRODH is induced by p53 under genotoxic stress and initiates apoptosis by both mitochondrial and death receptor pathways. Furthermore, POX/PRODH is induced by PPARgamma and its pharmacologic ligands, the thiazolidinediones. The anti-tumor effects of PPARgamma may be critically dependent on POX/PRODH. In addition, it is upregulated by nutrient stress through the mTOR pathway to maintain ATP levels. We propose that proline is made available as a stress substrate by the degradation of collagen in the microenvironmental extracellular matrix by matrix metalloproteinases. In a manner analogous to autophagy, this proline-dependent process for bioenergetics from collagen in extracellular matrix can be designated "ecophagy".
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