Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression
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Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression. / Wang, Qian; Bailey, Charles G; Ng, Cynthia; Tiffen, Jessamy; Thoeng, Annora; Minhas, Vineet; Lehman, Melanie L; Hendy, Stephen C; Buchanan, Grant; Nelson, Colleen C; Rasko, John E J; Holst, Jeff; Holst, Jens Juul.
In: Cancer Research, Vol. 71, No. 24, 2011, p. 7525-7536.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression
AU - Wang, Qian
AU - Bailey, Charles G
AU - Ng, Cynthia
AU - Tiffen, Jessamy
AU - Thoeng, Annora
AU - Minhas, Vineet
AU - Lehman, Melanie L
AU - Hendy, Stephen C
AU - Buchanan, Grant
AU - Nelson, Colleen C
AU - Rasko, John E J
AU - Holst, Jeff
AU - Holst, Jens Juul
PY - 2011
Y1 - 2011
N2 - L-Type amino acid transporters such as LAT1 and LAT3 mediate the uptake of essential amino acids. Here, we report that prostate cancer cells coordinate the expression of LAT1 and LAT3 to maintain sufficient levels of leucine needed for mTORC1 signaling and cell growth. Inhibiting LAT function was sufficient to decrease cell growth and mTORC1 signaling in prostate cancer cells. These cells maintained levels of amino acid influx through androgen receptor-mediated regulation of LAT3 expression and ATF4 regulation of LAT1 expression after amino acid deprivation. These responses remained intact in primary prostate cancer, as indicated by high levels of LAT3 in primary disease, and by increased levels of LAT1 after hormone ablation and in metastatic lesions. Taken together, our results show how prostate cancer cells respond to demands for increased essential amino acids by coordinately activating amino acid transporter pathways vital for tumor outgrowth.
AB - L-Type amino acid transporters such as LAT1 and LAT3 mediate the uptake of essential amino acids. Here, we report that prostate cancer cells coordinate the expression of LAT1 and LAT3 to maintain sufficient levels of leucine needed for mTORC1 signaling and cell growth. Inhibiting LAT function was sufficient to decrease cell growth and mTORC1 signaling in prostate cancer cells. These cells maintained levels of amino acid influx through androgen receptor-mediated regulation of LAT3 expression and ATF4 regulation of LAT1 expression after amino acid deprivation. These responses remained intact in primary prostate cancer, as indicated by high levels of LAT3 in primary disease, and by increased levels of LAT1 after hormone ablation and in metastatic lesions. Taken together, our results show how prostate cancer cells respond to demands for increased essential amino acids by coordinately activating amino acid transporter pathways vital for tumor outgrowth.
KW - Activating Transcription Factor 4
KW - Amino Acid Transport Systems, Basic
KW - Amino Acids
KW - Amino Acids, Cyclic
KW - Animals
KW - Biological Transport
KW - Blotting, Western
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Disease Progression
KW - Gene Expression Regulation, Neoplastic
KW - HEK293 Cells
KW - Humans
KW - Large Neutral Amino Acid-Transporter 1
KW - Male
KW - Mice
KW - Mice, Nude
KW - Neoplasm Transplantation
KW - Prostatic Neoplasms
KW - RNA Interference
KW - Receptors, Androgen
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Signal Transduction
KW - TOR Serine-Threonine Kinases
KW - Transplantation, Heterologous
U2 - 10.1158/0008-5472.CAN-11-1821
DO - 10.1158/0008-5472.CAN-11-1821
M3 - Journal article
C2 - 22007000
VL - 71
SP - 7525
EP - 7536
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 24
ER -
ID: 38531397