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

Research output: Contribution to journalJournal articleResearchpeer-review

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

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.
Original languageEnglish
JournalCancer Research
Volume71
Issue number24
Pages (from-to)7525-7536
Number of pages12
ISSN0008-5472
DOIs
Publication statusPublished - 2011

    Research areas

  • 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

ID: 38531397