Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth

Targeted cancer therapies, which act on specific cancer-associated molecular targets, are predominantly inhibitors of oncogenic kinases. While these drugs have achieved some clinical success, the inactivation of kinase signaling via stimulation of endogenous phosphatases has received minimal attention as an alternative targeted approach. Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. Our group previously developed a series of orally bioavailable small molecule activators of PP2A, termed SMAPs. We now report that SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse xenografts and transgenic models. Mechanistically, we found that SMAPs act by binding to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. These results show that PP2A can be activated in cancer cells to inhibit proliferation. Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins

Kinetics and Mechanisms of the Oxidation of Gaseous Sulfur Compounds

The problems associated with global climate change in general, and acid rain in particular, have led to a great deal of research on the atmospheric and combustion chemistry of sulfur. Developments over the last decade have led to significant progress in our understanding of the kinetics and mechanisms of the atmospheric oxidation chemistry of natural and anthropogenic sulfur. Rather less effort, however, has been placed on developing an understanding of sulfur combustion kinetics; the emphasis of mitigation research has instead been placed on removal of sulfur from fuels or development of scrubbing techniques to remove SO2 from stack gases