TY - JOUR
T1 - LAT1, a novel pharmacological target for the treatment of glioblastoma
AU - Cappoli, Natalia
AU - Jenkinson, Michael D.
AU - Dello Russo, Cinzia
AU - Dickens, David
PY - 2022
Y1 - 2022
N2 - The L-Type Amino Acid transporter, LAT1 (SLC7A5), has a crucial role in mediating amino acid uptake into the cells, thus modulating cell growth and proliferation as well as other intracellular functions. Different studies have reported a central role of LAT1 in glioblastoma development and progression, suggesting that the modulation of its activity could be a novel therapeutic strategy. LAT1 also has an important role in the peripheral immune system, by regulating the activation status of several immune cells through modulation of the mechanistic target of rapamycin kinase. In glioblastoma (GBM), the blood–brain barrier is disrupted, which allows the recruitment of peripheral immune cells to the tumour site. These cells, together with resident microglia, contribute to cancer growth and progression. Currently, little is known about the function of LAT1 in the reprogramming of the immune component of the tumour microenvironment in the context of GBM. In this article, we review the available data on the role of LAT1 in the regulation of GBM biology, including its potential role in the tumour microenvironment, particularly in infiltrating-peripheral immune cells and resident microglial cells. In addition, we review the available data on the main pharmacological inhibitors of LAT1, aiming to evaluate their possible role as novel therapeutics for GBM.
AB - The L-Type Amino Acid transporter, LAT1 (SLC7A5), has a crucial role in mediating amino acid uptake into the cells, thus modulating cell growth and proliferation as well as other intracellular functions. Different studies have reported a central role of LAT1 in glioblastoma development and progression, suggesting that the modulation of its activity could be a novel therapeutic strategy. LAT1 also has an important role in the peripheral immune system, by regulating the activation status of several immune cells through modulation of the mechanistic target of rapamycin kinase. In glioblastoma (GBM), the blood–brain barrier is disrupted, which allows the recruitment of peripheral immune cells to the tumour site. These cells, together with resident microglia, contribute to cancer growth and progression. Currently, little is known about the function of LAT1 in the reprogramming of the immune component of the tumour microenvironment in the context of GBM. In this article, we review the available data on the role of LAT1 in the regulation of GBM biology, including its potential role in the tumour microenvironment, particularly in infiltrating-peripheral immune cells and resident microglial cells. In addition, we review the available data on the main pharmacological inhibitors of LAT1, aiming to evaluate their possible role as novel therapeutics for GBM.
KW - Amino acid
KW - Glioblastoma
KW - LAT1
KW - LAT1-inhibitor JPH203
KW - Microglia
KW - Pharmacotherapy
KW - Amino acid
KW - Glioblastoma
KW - LAT1
KW - LAT1-inhibitor JPH203
KW - Microglia
KW - Pharmacotherapy
UR - http://hdl.handle.net/10807/210462
U2 - 10.1016/j.bcp.2022.115103
DO - 10.1016/j.bcp.2022.115103
M3 - Article
SN - 0006-2952
VL - 201
SP - 1
EP - 12
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
ER -