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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Wang Q,Bailey CG,Ng C,Tiffen J,Thoeng A,Minhas V,Lehman ML,Hendy SC,Buchanan G,Nelson CC,Rasko JE,Holst J

doi

10.1158/0008-5472.CAN-11-1821

subject

Has Abstract

pub_date

2011-12-15 00:00:00

pages

7525-36

issue

24

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-11-1821

journal_volume

71

pub_type

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