Proline dehydrogenase in cancer: apoptosis, autophagy, nutrient dependency and cancer therapy

Amino Acids. 2021 Dec;53(12):1891-1902. doi: 10.1007/s00726-021-03032-5. Epub 2021 Jul 20.

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.

Keywords: Apoptosis; Autophagy; Cancer; L-proline; PRODH; p53.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Autophagy / physiology*
  • Cellular Senescence / physiology
  • Humans
  • Neoplasms / metabolism*
  • Proline / metabolism*
  • Proline Oxidase / metabolism*
  • Signal Transduction / physiology

Substances

  • Proline
  • Proline Oxidase