L‑type amino acid transporter 1 expression is upregulated and associated with cellular proliferation in colorectal cancer

  • Authors:
    • Suguru Hayase
    • Kensuke Kumamoto
    • Katsuharu Saito
    • Yasuhide Kofunato
    • Yu Sato
    • Hirokazu Okayama
    • Kotaro Miyamoto
    • Shinji Ohki
    • Seiichi Takenoshita
  • View Affiliations

  • Published online on: October 6, 2017     https://doi.org/10.3892/ol.2017.7148
  • Pages:7410-7416
0

Abstract

Previous studies have shown that the L‑type amino acid transporter 1 (LAT1) is highly expressed in many types of cancer. Upregulated LAT1 expression is considered to be associated with cancer cell proliferation. In the present study, we investigated LAT1 expression in 210 patients with colorectal cancer (CRC) and 40 patients with colonic adenoma using an immunohistochemical method, and analyzed the associations between LAT1 expression and clinicopathological factors and prognosis. The biological significance of LAT1 was also examined under conditions with sub‑normal amounts of essential amino acids using colon cancer cell lines. High expression of LAT1 was observed in 152 of 210 CRC patients (72.4%) and 12 of 40 patients with colonic adenoma (30%), and this difference in the frequency of LAT1 expression between CRC and adenoma was significant (P<0.001). High expression of LAT1 was associated with venous invasion (P=0.027). The restriction of amino acids suppressed cell proliferation in CRC cells with higher LAT1 expression, while cellular proliferation was not suppressed in the cells expressing lower levels of LAT1. Mammalian target of rapamycin (mTOR) expression was also downregulated under restricted availability of amino acids, suggesting that the restriction of amino acids induced an antitumor effect through inhibition of the LAT1/mTOR pathway. In summary, the present study demonstrated that LAT1 expression is frequently upregulated in CRC and is associated with cancer cell proliferation via the mTOR pathway.

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December 2017
Volume 14 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Hayase, S., Kumamoto, K., Saito, K., Kofunato, Y., Sato, Y., Okayama, H. ... Takenoshita, S. (2017). L‑type amino acid transporter 1 expression is upregulated and associated with cellular proliferation in colorectal cancer. Oncology Letters, 14, 7410-7416. https://doi.org/10.3892/ol.2017.7148
MLA
Hayase, S., Kumamoto, K., Saito, K., Kofunato, Y., Sato, Y., Okayama, H., Miyamoto, K., Ohki, S., Takenoshita, S."L‑type amino acid transporter 1 expression is upregulated and associated with cellular proliferation in colorectal cancer". Oncology Letters 14.6 (2017): 7410-7416.
Chicago
Hayase, S., Kumamoto, K., Saito, K., Kofunato, Y., Sato, Y., Okayama, H., Miyamoto, K., Ohki, S., Takenoshita, S."L‑type amino acid transporter 1 expression is upregulated and associated with cellular proliferation in colorectal cancer". Oncology Letters 14, no. 6 (2017): 7410-7416. https://doi.org/10.3892/ol.2017.7148