Document Detail

How tumor cells employ extracellular phytate and MINPP1 to promote cell growth.
MedLine Citation:
PMID:  23186306     Owner:  NLM     Status:  Publisher    
Inositolhexakisphosphate (InsP6) is the most abundant inositolphosphate in mammalian cells with concentrations up to 50 µM. After necrosis of tumor cells InsP6 is released into the extracellular space where it is available for vital cells. Here, we show that extracellular InsP6, in low cellular concentrations (≤ 50 µM), stimulate tumor cell proliferation. Our study reveals that extracellular InsP6 (30 µM) can either be dephosphorylated to inositol, which is most likely transported into cells, or be directly endocytosed as a cationic complex in a receptor-independent manner. After cellular uptake InsP6 is also dephosphorylated to inositol in lysosomes, resulting in release of metal-phosphate. We identified the inositol-polyphosphate-phosphatase MINPP1 to be the mammalian phytase that catalyzes the first steps of InsP6 dephosphorylation. Prior to this finding the function of MINPP1 was enigmatic, now our data suggest that tumor cells use MINPP1 to release the micronutrients inositol and metal-phosphate from endocytosed InsP6 to enhance their mitogenic potential.
Sabine Windhorst; Hongying Lin; Christine Blechner; Werner Fanick; Laura Brandt; Maria Brehm; Georg W Mayr
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-28
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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