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

Abstract

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.

Potent‐By‐Design: Amino Acids Mimicking Porous Nanotherapeutics with Intrinsic Anticancer Targeting Properties

“…[ 38,39 ] Specifically, LAT‐1 plays a key role to supply EAA to growing tumor cells by activating progrowth signaling pathways such as the mammalian target of rapamycin (mTOR). [ 40 ] To examine whether if uptake of Nano‐pPAAM could be mediated via LAT‐1, we attempted to block its intracellular entry by using the LAT‐1 inhibitor, 2‐amino‐2‐norbornanecarboxylic acid (BCH). Inductively coupled plasma mass spectrometry (ICP–MS) was employed to determine the intracellular content of Si in MDA‐MB‐231 cells with and without BCH (10 × 10 −3 m ).…”

Expression of L-type amino acid transporter 1 as a molecular target for prognostic and therapeutic indicators in bladder carcinoma

“…Amino acids are indispensable for the proliferation of cancer cells, and transported to the cell by a selective transporter on the plasma membrane 6 . Several lines of evidence have shown that amino acid transporters are upregulated in cancer cells while supporting large-scale growth and reproduction [7][8][9] . L-type amino acid transporter 1 (LAT1) transports neutral amino acids into cells in a Na + -independent manner 10 .…”

“…L-type amino acid transporter 1 (LAT1) transports neutral amino acids into cells in a Na + -independent manner 10 . LAT1-mediated leucine uptake interactions with cell growth, transcription, and translation through the mammalian Target of Rapamycin (mTOR) signaling pathway 8,9 . Because many reports have shown that LAT1 is highly expressed in cancer cells, LAT1 has become a novel target for cancers [11][12][13] .…”

Targeting L-type amino acid transporter 1 in innate and adaptive T cells efficiently controls skin inflammation

“…16 However, LAT1 is the main L-leucine (L-Leu) transporter expressed in T-cell receptor (TCR)-activated T cells 17 and natural killer cells. 18 The expression of LAT1 is increased in many cancer cells, 19 including malignant skin lesions. 20 LAT1 is the main mediator of L-Leu uptake in malignant cells, and its usefulness as a target to inhibit cancer proliferation has been explored.…”