biostudies-literatureChen RQNCI NIH HHS2663-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC2697620biostudies-literatureUnknown69(6)Because the mammalian target of rapamycin (mTOR) pathway is commonly deregulated in human cancer, mTOR inhibitors, rapamycin and its derivatives, are being actively tested in cancer clinical trials. Clinical updates indicate that the anticancer effect of these drugs is limited, perhaps due to rapamycin-dependent induction of oncogenic cascades by an as yet unclear mechanism. As such, we investigated rapamycin-dependent phosphoproteomics and discovered that 250 phosphosites in 161 cellular proteins were sensitive to rapamycin. Among these, rapamycin regulated four kinases and four phosphatases. A siRNA-dependent screen of these proteins showed that AKT induction by rapamycin was attenuated by depleting cellular CDC25B phosphatase. Rapamycin induces the phosphorylation of CDC25B at Serine375Cancer researchCDC25B mediates rapamycin-induced oncogenic responses in cancer cells.PMC2697620CA079871CA114059R01 CA079871-07R01 CA079871R01 CA114059-03R01 CA114059Lee JDCantin GYates JRYang QKLu BWChen RQYi WChen YLFearns CfalseCDC25B mediates rapamycin-induced oncogenic responses in cancer cells.Because the mammalian target of rapamycin (mTOR) pathway is commonly deregulated in human cancer, mTOR inhibitors, rapamycin and its derivatives, are being actively tested in cancer clinical trials. Clinical updates indicate that the anticancer effect of these drugs is limited, perhaps due to rapamycin-dependent induction of oncogenic cascades by an as yet unclear mechanism. As such, we investigated rapamycin-dependent phosphoproteomics and discovered that 250 phosphosites in 161 cellular proteins were sensitive to rapamycin. Among these, rapamycin regulated four kinases and four phosphatases. A siRNA-dependent screen of these proteins showed that AKT induction by rapamycin was attenuated by depleting cellular CDC25B phosphatase. Rapamycin induces the phosphorylation of CDC25B at Serine3752009-01-01T00:00:00Z2009 Mar2025-04-26T00:30:03.582Z2019-03-27T00:23:00ZS-EPMC26976201927636810.1158/0008-5472.can-08-322210.1158/0008-5472.CAN-08-3222