Proline metabolism in cancer

Cancer cells often change their metabolism to support uncontrolled proliferation. Proline is the only proteogenic secondary amino acid that is abundant in the body. Recent studies have shown that proline metabolism plays an important role in metabolic reprogramming and affects the occurrence and development of cancer. Proline metabolism is related to ATP production, protein and nucleotide synthesis, and redox homeostasis in tumor cells. Proline can be synthesized by aldehyde dehydrogenase family 18 member A1 (ALDH18A1) and delta1-pyrroline-5-carboxylate reductase (PYCR), up-regulating ALDH18A1 and PYCR can promote the proliferation and invasion of cancer cells. As the main storage of proline, collagen can influence cancer cells proliferation, invasion, and metastasis. Its synthesis depends on the hydroxylation of proline catalyzed by prolyl 4-hydroxylases (P4Hs), which will affect the plasticity and metastasis of cancer cells. The degradation of proline occurs in the mitochondria and involves an oxidation step catalyzed by proline dehydrogenase/proline oxidase (PRODH/POX). Proline catabolism has a dual role in cancer, linking apoptosis with the survival and metastasis of cancer cells. In addition, it has been demonstrated that the regulation of proline metabolic enzymes at the genetic and post-translational levels is related to cancer. This article reviews the role of proline metabolic enzymes in cancer proliferation, apoptosis, metastasis, and development. Research on proline metabolism may provide a new strategy for cancer treatment.