InsP6 [Ins(1,2,3,4,5,6)P6; phytate] is the most abundant inositol phosphate in mammalian cells with cytosolic/nuclear concentrations of up to 50 μM. We noticed that InsP6 in culture medium at a concentration of ≤50 μM significantly stimulates H1299 tumour cell growth, whereas larger concentrations of InsP6 inhibit growth. A detailed study of the fate of 30 μM InsP6 added to H199 cells revealed a major fraction of InsP6 initially precipitates as cell-surface metal complexes, but becomes slowly re-solubilized by extracellular dephosphorylation first to InsP3 isomers and subsequently to free myo-inositol. The precipitated metal–InsP6 complex is endocytosed in a receptor-independent but intact-glycocalyx-dependent manner and appears in lysosomes, where it is immediately dephosphorylated to Ins(1,2,4,5,6)P5 and very slowly to free inositol. By RNA knockdown, we identified secreted and lysosome targeted MINPP1 (multiple inositol-polyphosphate phosphatase 1), the mammalian 3-phytase, to be essentially involved both in extracellular and in lysosomal InsP6 dephosphorylation. The results of the present study indicate that tumour cells employ this enzyme to utilize the micronutrients myo-inositol and metal-phosphate when encountering extracellular InsP6 and thus to enhance their growth potential.
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Research Article|
January 24 2013
Tumour cells can employ extracellular Ins(1,2,3,4,5,6)P6 and multiple inositol-polyphosphate phosphatase 1 (MINPP1) dephosphorylation to improve their proliferation
Sabine Windhorst;
Sabine Windhorst
1
1Institut für Biochemie und Signaltransduktion, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany
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Hongying Lin;
Hongying Lin
1
1Institut für Biochemie und Signaltransduktion, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany
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Christine Blechner;
Christine Blechner
1Institut für Biochemie und Signaltransduktion, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany
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Werner Fanick;
Werner Fanick
1Institut für Biochemie und Signaltransduktion, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany
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Laura Brandt;
Laura Brandt
1Institut für Biochemie und Signaltransduktion, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany
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Maria A. Brehm;
Maria A. Brehm
1Institut für Biochemie und Signaltransduktion, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany
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Georg W. Mayr
Georg W. Mayr
2
1Institut für Biochemie und Signaltransduktion, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany
2To whom correspondence should be addressed (email mayr@uke.uni-hamburg.de).
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Publisher: Portland Press Ltd
Received:
October 03 2012
Revision Received:
November 15 2012
Accepted:
November 28 2012
Accepted Manuscript online:
November 28 2012
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 450 (1): 115–125.
Article history
Received:
October 03 2012
Revision Received:
November 15 2012
Accepted:
November 28 2012
Accepted Manuscript online:
November 28 2012
Citation
Sabine Windhorst, Hongying Lin, Christine Blechner, Werner Fanick, Laura Brandt, Maria A. Brehm, Georg W. Mayr; Tumour cells can employ extracellular Ins(1,2,3,4,5,6)P6 and multiple inositol-polyphosphate phosphatase 1 (MINPP1) dephosphorylation to improve their proliferation. Biochem J 15 February 2013; 450 (1): 115–125. doi: https://doi.org/10.1042/BJ20121524
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