Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression

Qian Wang; Charles G Bailey; Cynthia Ng; Jessamy Tiffen; Annora Thoeng; Vineet Minhas; Melanie L Lehman; Stephen C Hendy; Grant Buchanan; Colleen C Nelson; John E J Rasko; Jeff Holst; Jens Juul Holst

doi:10.1158/0008-5472.can-11-1821

Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression

Qian Wang, Charles G Bailey, Cynthia Ng, Jessamy Tiffen, Annora Thoeng, Vineet Minhas, Melanie L Lehman, Stephen C Hendy, Grant Buchanan, Colleen C Nelson, John E J Rasko, Jeff Holst, Jens Juul Holst

104 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Cancer Research
Vol/bind	71
Udgave nummer	24
Sider (fra-til)	7525-7536
Antal sider	12
ISSN	0008-5472
DOI	https://doi.org/10.1158/0008-5472.can-11-1821
Status	Udgivet - 15 dec. 2011

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10.1158/0008-5472.can-11-1821

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https://cancerres.aacrjournals.org/content/canres/71/24/7525.full.pdf

Citationsformater

Wang, Q., Bailey, C. G., Ng, C., Tiffen, J., Thoeng, A., Minhas, V., Lehman, M. L., Hendy, S. C., Buchanan, G., Nelson, C. C., Rasko, J. E. J., Holst, J., & Holst, J. J. (2011). Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression. Cancer Research, 71(24), 7525-7536. https://doi.org/10.1158/0008-5472.can-11-1821

Wang, Q, Bailey, CG, Ng, C, Tiffen, J, Thoeng, A, Minhas, V, Lehman, ML, Hendy, SC, Buchanan, G, Nelson, CC, Rasko, JEJ, Holst, J & Holst, JJ 2011, 'Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression', Cancer Research, bind 71, nr. 24, s. 7525-7536. https://doi.org/10.1158/0008-5472.can-11-1821

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title = "Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression",

abstract = "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.",

keywords = "Activating Transcription Factor 4, Amino Acid Transport Systems, Basic, Amino Acids, Amino Acids, Cyclic, Animals, Biological Transport, Blotting, Western, Cell Line, Tumor, Cell Proliferation, Disease Progression, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Large Neutral Amino Acid-Transporter 1, Male, Mice, Mice, Nude, Neoplasm Transplantation, Prostatic Neoplasms, RNA Interference, Receptors, Androgen, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, TOR Serine-Threonine Kinases, Transplantation, Heterologous",

author = "Qian Wang and Bailey, {Charles G} and Cynthia Ng and Jessamy Tiffen and Annora Thoeng and Vineet Minhas and Lehman, {Melanie L} and Hendy, {Stephen C} and Grant Buchanan and Nelson, {Colleen C} and Rasko, {John E J} and Jeff Holst and Holst, {Jens Juul}",

year = "2011",

month = dec,

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doi = "10.1158/0008-5472.can-11-1821",

language = "English",

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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 - 2011/12/15

Y1 - 2011/12/15

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

SN - 0008-5472

VL - 71

SP - 7525

EP - 7536

JO - Cancer Research

JF - Cancer Research

IS - 24

ER -

Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression

Abstract

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