Androgen Receptor and Nutrient Signaling Pathways Coordinate the Demand for Increased Amino Acid Transport during Prostate Cancer Progression

被引：149

作者：

Wang, Qian ^{[1
,2
]}

Bailey, Charles G. ^{[2
,4
]}

Ng, Cynthia ^{[2
]}

Tiffen, Jessamy ^{[1
,2
]}

Thoeng, Annora ^{[2
]}

Minhas, Vineet ^{[1
,2
]}

Lehman, Melanie L. ^{[7
]}

Hendy, Stephen C. ^{[7
]}

Buchanan, Grant ^{[5
]}

Nelson, Colleen C. ^{[6
,7
]}

Rasko, John E. J. ^{[2
,3
,4
]}

Holst, Jeff ^{[1
,2
,4
]}

机构：

[1] Centenary Inst, Origins Canc Lab, Newtown, NSW 2042, Australia

[2] Centenary Inst, Gene & Stem Cell Therapy Program, Newtown, NSW 2042, Australia

[3] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia

[4] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia

[5] Univ Adelaide, Mol Ageing Lab, Adelaide, SA, Australia

[6] Queensland Univ Technol, Australian Prostate Canc Res Ctr Queensland, Brisbane, Qld 4001, Australia

[7] Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada

来源：

CANCER RESEARCH | 2011年 / 71卷 / 24期

关键词：

TUMOR-SUPPRESSOR; RAG GTPASES; MTOR; EXPRESSION; GROWTH; PTEN; CARCINOMA; IDENTIFICATION; TRANSCRIPTION; METABOLISM;

D O I：

10.1158/0008-5472.CAN-11-1821

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Cancer Res; 71(24); 7525-36. (C) 2011 AACR.

引用

页码：7525 / 7536

页数：12

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