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View the Table of Contents for the May 1 issue of Cancer Research.
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The NF2 tumor suppressor gene encodes an intracellular membrane-associated protein, merlin, which couples glycoproteins to the actin cytoskeleton. Merlin suppresses PI3K/Akt signaling and, in turn, Akt phosphorylates merlin, triggering its degradation. Okada and colleagues report that merlin associates directly with phosphatidylinositols and that phosphorylation by Akt inhibits its proapoptotic activity and promotes cell migration. This dual regulation provides a novel mechanism explaining how oncogenic PI3K signaling regulates merlin’s tumor suppressive activity via both Akt and phosphatidylinositol lipids.
Hu et al. Page 4067 The five-member Smyd family is involved in breast cancer development and tumorigenesis through their lysine methyltransferase activity for histone and nonhistone proteins. Hu and colleagues found that the disruption of one allele of Smyd4 gene through chromosome rearrangement leads to tumorigenesis of mammary epithelial cells. Re-expression of Smyd4 inhibits tumor development in nude mice. The authors also demonstrate that Smyd4 suppresses the expression of Pdgfr-α. These results, together with the observation that Smyd4 is silenced in a proportion of primary breast cancers, support the idea that Smyd4 functions as a tumor suppressor.
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