Amino acid transporters as emerging therapeutic targets in cancer

Cancer Sci. 2021 Aug;112(8):2958-2965. doi: 10.1111/cas.15006. Epub 2021 Jun 28.

Abstract

Amino acids are indispensable nutrients for both normal and cancer cells. Cancer cells are unable to synthesize essential amino acids as well as some non-essential amino acids adequately to support rapid proliferation, and must take up amino acids from the surroundings. To meet the increased demand for the amino acid needed for proliferation, high levels of amino acid transporters are expressed on the surface of cancer cells. Cancer cells utilize amino acids to synthesize proteins and nucleotides, as well as to obtain energy. In addition, amino acids are known to play pathological roles in cancer cells. Interestingly, breast cancer cells limit the use of amino acids for cell proliferation based on amino acid availability, which depends on estrogen receptor status. Here, we present a summarized literature review of novel amino acid functions in cancer cells. This review organizes the available knowledge on 2 amino acid transporters, SLC7A5 and SLC7A11, which are considered essential for breast cancer cell growth in a cell-dependent manner. In particular, we propose the glutamine recycling model to clarify the mechanism underlying aberrant SLC7A5 activation. Finally, we overview the pathological significances of SLC7A5 and SLC7A11 in cancer tissues.

Keywords: amino acid transporter; breast cancer; cell proliferation; cystine uptake; leucine uptake.

Publication types

  • Review

MeSH terms

  • Amino Acid Transport System y+ / metabolism*
  • Amino Acids / metabolism
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Cell Proliferation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Large Neutral Amino Acid-Transporter 1 / metabolism*
  • Molecular Targeted Therapy

Substances

  • Amino Acid Transport System y+
  • Amino Acids
  • Antineoplastic Agents
  • Large Neutral Amino Acid-Transporter 1
  • SLC7A11 protein, human
  • SLC7A5 protein, human