Cellular Signaling of Amino Acid Metabolism in Prostate Cancer

Int J Mol Sci. 2025 Jan 17;26(2):776. doi: 10.3390/ijms26020776.

Abstract

Prostate cancer is one of the most common malignancies affecting men worldwide and a leading cause of cancer-related mortality, necessitating a deeper understanding of its underlying biochemical pathways. Similar to other cancer types, prostate cancer is also characterised by aberrantly activated metabolic pathways that support tumour development, such as amino acid metabolism, which is involved in modulating key physiological and pathological cellular processes during the progression of this disease. The metabolism of several amino acids, such as glutamine and methionine, crucial for tumorigenesis, is dysregulated and commonly discussed in prostate cancer. And the roles of some less studied amino acids, such as histidine and glycine, have also been covered in prostate cancer studies. Aberrant regulation of two major signalling pathways, mechanistic target of rapamycin (mTOR) and general amino acid control non-depressible 2 (GCN2), is a key driver of reshaping the amino acid metabolism landscape in prostate cancer. By summarising our current understanding of how amino acid metabolism is modulated in prostate cancer, here, we provide further insights into certain potential therapeutic targets for managing prostate cancer through metabolic interventions.

Keywords: GCN2; amino acid; mTOR; metabolic reprogramming; prostate cancer.

Publication types

  • Review

MeSH terms

  • Amino Acids* / metabolism
  • Animals
  • Humans
  • Male
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Protein Serine-Threonine Kinases
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Amino Acids
  • TOR Serine-Threonine Kinases
  • MTOR protein, human
  • EIF2AK4 protein, human
  • Protein Serine-Threonine Kinases