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Ryan, too, eventually paid a price, losing his job and being replaced by Pia Sundhage of Sweden.
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This suggests that loss of EGFR and IGFR expression by PIAs is a common cellular response.
These data suggest that ceramide generation underlies the release of nanovesicles from cancer cells mediated by PIAs and Per.
Since AKT activity does not seem to be reduced significantly by PIAs under normal serum condition, we looked for other potential effector molecules.
However, pretreatment with a proteasome inhibitor (Supplementary Figure S2A) or a lysosome inhibitor (Supplementary Figure S2B) failed to block the loss of EGFR or IGFR by PIAs.
Stimulation of nanovesicle release by PIAs or Per did not depend on Akt inhibition, which agrees with previous studies demonstrating PIAs fuction through a distinct mechanism from other PI3K/Akt pathway inhibitors and target other proteins in addition to Akt.
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