Document Detail


Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression.
MedLine Citation:
PMID:  22007000     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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. Inhibitiing 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.
Authors:
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 Ej Rasko; Jeff Holst
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-17
Journal Detail:
Title:  Cancer research     Volume:  -     ISSN:  1538-7445     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Gene and Stem Cell Therapy Program, Centenary Institute.
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