High Dietary Inorganic Phosphate Increases Lung Tumorigenesis and Alters Akt Signaling

Posted by Jim:

High Dietary Inorganic Phosphate Increases Lung Tumorigenesis and Alters Akt Signaling — Jin et al. 179 1: 59 — American Journal of Respiratory and Critical Care Medicine.

Here’s a very exciting paper reporting a study I have been thinking of doing myself for a long time.  I wish I had been the one to do it, but it’s great to see it with my own eyes.

They grew up cancer-susceptible mice with two diets (regular, nutrient sufficient with 0.5% Pi vs. high P in which dietary P was 2x higher, 1%Pi).  Then they measured number and size of lung tumors, serum Pi levels, as well as various cellular responses, including changes in Pi transporters and indicators of cellular proliferation rate.

Animals on the high P diet had:

-higher serum Pi concentrations

– 2x (!) higher number of tumors

-larger tumors

-2x higher expression of Pi membrane transporters

-2x higher levels for expression of cell-cycle indicators

-5x higher levels of expression of cap-dependent protein translation (e.g. ribosome production?), a strong indicator of cell proliferation

All in all, this is extremely consistent with our ideas of r/K selection in human cancer, as lung tumors (in our PLOS ONE paper link) have 2-3 times higher P content than normal tissue and seem to have evolved into tumors via pathways of mutations that result in more rapid cell proliferation (rather than ones that lead to decreased apoptosis or senescence).

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3 responses to “High Dietary Inorganic Phosphate Increases Lung Tumorigenesis and Alters Akt Signaling

  1. Yeah, this is truly cool and worth repeating for other tissues/tumors. Perhaps targeted Fe3+ or other P-binders would be the ultimate cure?

  2. Thanks Dag. We have an NIH EUREKA proposal out right now to study tumor evolution in a stoichiometric context, using Avastin-resistance in glioblastoma as a test bed. If funded perhaps we can find a way to manipulate P supply to test these ideas. I must say I never thought I’d see evidence as strong as this supporting the tumor P-limitation hypothesis in my lifetime! So, this paper has me quite energized.

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