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Several articles have concluded that associations between high cholesterol and premature death are lacking and advocate revision of current guidance advising low consumption (

We have recently recapitulated metastasis of human PTEN/TP53–mutant prostate cancer in the mouse using the RapidCaP system. Surprisingly, we found that this metastasis is driven by MYC, and not AKT, activation. Here, we show that cell–cell communication by IL6 drives the AKT–MYC switch through activation of the AKT-suppressing phosphatase PHLPP2, when PTEN and p53 are lost together, but not separately. IL6 then communicates a downstream program of STAT3-mediated MYC activation, which drives cell proliferation. Similarly, in tissues, peak proliferation in Pten/Trp53–mutant primary and metastatic prostate cancer does not correlate with activated AKT, but with STAT3/MYC activation instead. Mechanistically, MYC strongly activates the AKT phosphatase PHLPP2 in primary cells and prostate cancer metastasis. We show genetically that Phlpp2 is essential for dictating the proliferation of MYC-mediated AKT suppression. Collectively, our data reveal competition between two proto-oncogenes, MYC and AKT, which ensnarls the Phlpp2 gene to facilitate MYC-driven prostate cancer metastasis after loss of Pten and Trp53. Significance: Our data identify IL6 detection as a potential causal biomarker for MYC-driven metastasis after loss of PTEN and p53. Second, our finding that MYC then must supersede AKT to drive cell proliferation points to MYC inhibition as a critical part of PI3K pathway therapy in lethal prostate cancer. Cancer Discov; 5(6); 636–51. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 565

Background Currently available chronic myeloid leukaemia (CML) survival reports have originated from more affluent countries. Herein we report the entire country data on incidence and survival of CML, as well as penetrance of tyrosine kinase inhibitors (TKIs) in Lithuania. Methods We analyzed all patients (N = 601) from the national haematological disease monitoring system who were diagnosed with CML between 2000 and 2013. Crude (CR) and age-standardized (weighted) (ASW(R)) incidence and mortality rates, as well as 1-, 5-, and 10-year relative survival rates (RSR) were calculated. Information on TKI penetration is also reported. Results Throughout the entire 2000–2013 period the median age at diagnosis of CML patients was 62 years. The respective incidence and mortality CRs were 1.28 and 0.78, both characterized by decreasing trends over the observation period. A 5-year RSR increased from 0.33 [95 % CI, 0.27–0.40] in 2000–2004 to 0.55 [95 % CI, 0.47–0.63] in 2005–2009. However, the respective 5-year RSRs for patients aged 65–74 and ≥75 were only 0.33 [95 % CI, 0.24–0.42] and 0.18 [95 % CI 0.07–0.23] during the entire study period. TKI penetrance for CML patients grew from 1.5 % in 2000–2004 to 30.6 % in 2005–2009 and 69.1 % in 2010–2013. TKI penetrance was low in the older age groups (60 % for the 65–74 and 19 % for the ≥75 patient group, in 2010–2013). Conclusion Relative CML survival in Lithuania steadily improved and paralleled the increase in TKI treatment availability. Patients above 64 years rarely received TKIs and their relative survival remained low throughout the observation period. The latency of TKI availability may have influenced the survival trends. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2238-9) contains supplementary material, which is available to authorized users.