Scientists from Cold Spring Harbor have published their new research progress , which prove that how immune system cytokines IL-6 drives invasiveness and play important role in prostate therapy. This study was published on Cancer Discovery.
Prostate cancer(PC) is one of the most prevalent cancers among men and it is estimated that in 2014 there will be 233,000 new PC cases, making up 14% of all new cancer cases , causing an estimated 29,480 deaths in United States alone. Although mortality rates have been decreasing, PC is still among the most common causes of cancers-related death and malignancy in men in developed counties.
In this study, scientists show that cell-cell communication by II6 drives the Akt-Myc switch through activation of the Akt-suppressing phosphatase Phlpp2, when Pten and p53 are lost together, but separately. II6 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 PC does not correlate with activated Akt, but with Stat3/ Myc activation instead. Mechanistically, Myc strongly activates the Akt phosphatase Phlpp2 in primary cells and PC metastasis. They show genetically that Phlpp2 is essential for dictating proliferation of Myc-mediated Aktsuppression。
Collectively, their data reveal competition between two proto-oncogenes: Myc and Akt, which ensnarls the Phlpp2 gene to facilitate Myc-driven PC metastasis after loss of Pten and Trp53.
Nowak D G, Cho H, Herzka T, et al. Myc drives Pten/p53-deficient proliferation and metastasis due to Il6-secretion and Akt-suppression via Phlpp2[J]. Cancer discovery, 2015: CD-14-1113.