EDC3 phosphorylation regulates growth and invasion through controlling P‐body formation and dynamics

Regulation of mRNA stability and translation plays a critical role in determining protein abundance within cells. Processing bodies (P‐bodies) are critical regulators of these processes. Here, we report that the Pim1 and 3 protein kinases bind to the P‐body protein enhancer of mRNA decapping 3 (EDC3) and phosphorylate EDC3 on serine (S)161, thereby modifying P‐body assembly. EDC3 phosphorylation is highly elevated in many tumor types, is reduced upon treatment of cells with kinase inhibitors, and blocks the localization of EDC3 to P‐bodies. Prostate cancer cells harboring an EDC3 S161A mutation show markedly decreased growth, migration, and invasion in tissue culture and in xenograft models. Consistent with these phenotypic changes, the expression of integrin β1 and α6 mRNA and protein is reduced in these mutated cells. These results demonstrate that EDC3 phosphorylation regulates multiple cancer‐relevant functions and suggest that modulation of P‐body activity may represent a new paradigm for cancer treatment.     

THE TOXICITY OF CERTAIN SYNTHETIC ORGANIC COMPOUNDS TO THE FRUIT-TREE RED-SPIDER MITE

The acaricidal activity of ninety synthetic organic compounds has been investigated in the laboratory. Considerable differences were found between the winter eggs, the summer eggs and the adult female stages of the fruit-tree red-spider mite (Meta-tetranychus ulmi (Koch)) in their susceptibility to many of the compounds but two substances, namely azoxybenzene and n-dodecyl thiocyanate, were appreciably toxic to all three stages. Of the compounds showing promise against summer eggs and mites, bis-( p -chlorophenyl) methyl carbinol and 4-chloroazobenzene were the best, being highly toxic to both summer stages. Of the remainder, diphenylsulphone, 4-chlorodiphenylsulphone, azobenzene and hydrazobenzene were highly ovicidal, while C₁₂-C₁₃ alkyl thiocyanates and sec .-dodecyl thiocyanate gave high kills of the adult female mite.
Relationships between molecular structure and acaricidal activity have been sought. In a series of compounds characterized by the presence of two benzene nuclei connected by certain bridging groups, it has been found that activity to the summer stages of the mite can be influenced by alterations to the bridging group and by substitution in the benzene nuclei. Maximum activity appears to be associated with chlorine substitution in the para position in one nucleus and also with compounds of this type having unsubstituted nuclei.