Cationic amino acid transporter PQLC2 is a potential therapeutic target in gastric cancer

Cancer Sci. 2019 Apr;110(4):1453-1463. doi: 10.1111/cas.13966. Epub 2019 Mar 19.

Abstract

Tumor cells overexpress amino acid transporters to meet the increased demand for amino acids. PQ loop repeat-containing (PQLC)2 is a cationic amino acid transporter that might be involved in cancer progression. Here, we show that upregulation of PQLC2 is critical to gastric cancer (GC) development in vitro and in vivo. Both PQLC2 mRNA and protein were overexpressed in GC tissues, especially of the diffuse type. Overexpression of PQLC2 promoted cell growth, anchorage independence, and tumor formation in nude mice. This was due to activation of MEK/ERK1/2 and PI3K/AKT signaling. Conversely, PQLC2 knockdown caused growth arrest and cell death of cancer cells and suppressed tumor growth in a mouse xenograft model. These results suggest that targeting PQLC2 is an effective strategy for GC treatment.

Keywords: PQLC2; gastric cancer; metastasis; therapeutic target; tumor formation.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amino Acid Transport Systems, Basic / antagonists & inhibitors
  • Amino Acid Transport Systems, Basic / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Gene Silencing
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Amino Acid Transport Systems, Basic
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • SLC66A1 protein, human