2. Academic Validation
  3. Efficacy of system l amino acid transporter 1 inhibition as a therapeutic target in esophageal squamous cell carcinoma

Efficacy of system l amino acid transporter 1 inhibition as a therapeutic target in esophageal squamous cell carcinoma

  • Cancer Sci. 2016 Oct;107(10):1499-1505. doi: 10.1111/cas.13021.
Yasuhiro Ohshima 1,  Kyoichi Kaira 2,  Aiko Yamaguchi 3,  Noboru Oriuchi 4,  Hideyuki Tominaga 4,  Shushi Nagamori 5,  Yoshikatsu Kanai 5,  Takehiko Yokobori 6,  Tatsuya Miyazaki 7,  Takayuki Asao 2,  Yoshito Tsushima 8,  Hiroyuki Kuwano 7,  Noriko S Ishioka 9
Affiliations

Affiliations

  • 1 Department of Radiation-Applied Biology Research, Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology, Takasaki, Japan. b16gradmmptimp@yahoo.co.jp.
  • 2 Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Maebashi, Japan.
  • 3 Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, Maebashi, Japan.
  • 4 Advanced Clinical Research Center, Fukushima Medical University, Fukushima, Japan.
  • 5 Division of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Suita, Japan.
  • 6 Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan.
  • 7 Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
  • 8 Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
  • 9 Department of Radiation-Applied Biology Research, Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology, Takasaki, Japan.
PMID: 27465934 DOI: 10.1111/cas.13021
Abstract

System l amino acid transporter 1 (LAT1) is highly expressed in various types of human Cancer, and contributes to Cancer growth and survival. Recently, we have shown that LAT1 expression is closely related to the growth and aggressiveness of esophageal Cancer, and is an independent marker of poor prognosis. However, it remains unclear whether LAT1 inhibition could suppress esophageal Cancer growth. In this study, we investigated the tumor-suppressive effects of the inhibition of LAT1. Both LAT1 and CD98, which covalently associates to LAT1 on the membrane, were expressed in human esophageal Cancer cell lines KYSE30 and KYSE150. Quantitative PCR analysis showed that the expression of LAT1 was much higher than other subtypes of LAT. A selective inhibitor of LAT, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), suppressed cellular uptake of l-14 C-leucine and cell proliferation in a dose-dependent manner. It also suppressed phosphorylation of mammalian target of rapamycin, 4E-BP1, and p70S6K protein, and induced cell cycle arrest at G1 phase. These results suggest that suppression of both mammalian target of rapamycin signaling and cell cycle progression is involved in BCH-induced growth inhibition. In tumor-bearing mice, daily treatment with BCH significantly delayed tumor growth and decreased glucose metabolism, indicating that LAT1 inhibition potentially suppresses esophageal Cancer growth in vivo. Thus, our results suggest that LAT1 inhibition could be a promising molecular target for the esophageal Cancer therapy.

Keywords

2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid; esophageal cancer; mammalian target of rapamycin; molecular target; system l amino acid transporter 1.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-108540
    99.13%, LAT1抑制剂
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