Expression of L-type amino acid transporter 1 is a poor prognostic factor for Non-Hodgkin's lymphoma

Sci Rep. 2021 Nov 4;11(1):21638. doi: 10.1038/s41598-021-00811-8.

Abstract

L-type neutral amino acid transporter 1 (LAT1) is a heterodimeric membrane transport protein involved in neutral amino acid transport. LAT1 is highly expressed in various malignant solid tumors and plays an essential role in cell proliferation. However, its role in malignant lymphoma remains unknown. Here, we evaluated LAT1 expression level in tissues from 138 patients with Non-Hodgkin lymphoma (NHL). Overexpression of LAT1 was confirmed in all types of NHL and we found that there is a significant correlation between the level of LAT1 expression and lymphoma grade. The LAT1 expression was higher in aggressive types of lymphomas when compared with static types of lymphomas, suggesting that active tumor proliferation requires nutrient uptake via LAT1. The expression level of LAT1 was inversely correlated with patients' survival span. Furthermore, pharmacological inhibition of LAT1 by a specific inhibitor JPH203 inhibits lymphoma cell growth. In conclusion, our study demonstrated that LAT1 expression can be used as a prognostic marker for patients with NHL and targeting LAT1 by JPH203 can be a novel therapeutic modality for NHL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Transport System L / metabolism
  • Amino Acid Transport Systems / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Large Neutral Amino Acid-Transporter 1 / genetics*
  • Large Neutral Amino Acid-Transporter 1 / metabolism
  • Lymphoma, Non-Hodgkin / metabolism*
  • Lymphoma, Non-Hodgkin / physiopathology
  • Male
  • Middle Aged
  • Prognosis
  • Transcriptome / genetics

Substances

  • Amino Acid Transport System L
  • Amino Acid Transport Systems
  • Large Neutral Amino Acid-Transporter 1
  • SLC7A5 protein, human