Sin3a acts through a multi-gene module to regulate invasion in Drosophila and human tumors.

Chromatin remodeling proteins regulate multiple aspects of cell homeostasis, making them ideal candidates for misregulation in transformed cells. Here, we explore Sin3A, a member of the Sin3 family of proteins linked to tumorigenesis that are thought to regulate gene expression through their role as histone deacetylases (HDACs). We identified Drosophila Sin3a as an important mediator of oncogenic Ret receptor in a fly model of Multiple Endocrine Neoplasia Type 2. Reducing Drosophila Sin3a activity led to metastasis-like behavior and, in the presence of Diap1, secondary tumors distant from the site of origin. Genetic and Chip-Seq analyses identified previously undescribed Sin3a targets including genes involved in cell motility and actin dynamics, as well as signaling pathways including Src, Jnk and Rho. A key Sin3a oncogenic target, PP1B, regulates stability of ß-Catenin/Armadillo: the outcome is to oppose T-cell factor (TCF) function and Wg/Wnt pathway signaling in both fly and mammalian cancer cells. Reducing Sin3A strongly increased the invasive behavior of A549 human lung adenocarcinoma cells. We show that Sin3A is downregulated in a variety of human tumors and that Src, JNK, RhoA and PP1B/ß-Catenin are regulated in a manner analogous to our Drosophila models. Our data suggest that Sin3A influences a specific step of tumorigenesis by regulating a module of genes involved in cell invasion. Tumor progression may commonly rely on such 'modules of invasion' under the control of broad transcriptional regulators.

An investigation into alternative reservoirs of canine leishmaniasis on the endemic island of Mallorca (Spain).

The role of wild and free-roaming domestic carnivores as a reservoir of Leishmania infantum was investigated on the Mediterranean island of Mallorca (Balearic Islands, Spain), an endemic area for this disease. Serum, blood and/or spleen samples from 169 animals [48 dogs from a kennel, 86 wild-caught feral cats, 23 pine martens (Martes martes), 10 common genets (Genetta genetta) and two weasels (Mustela nivalis)] were analysed. Seroprevalence determined by Western blotting was 38% in dogs and 16% in feral cats, while the prevalence of infection determined by PCR was 44% in dogs, 26% in cats, 39% in pine martens and 10% in genets. This is the first report of infection by L. infantum in the pine marten or any other member of the Mustelidae family. Restriction fragment length polymorphism (RFLP) analysis found 33 different patterns in 23 dogs, 14 cats and three martens. Two patterns were shared by dogs and cats, two by different cats, and one by different dogs. Patterns were different to those previously reported in carnivores from peninsular Spain. No external lesions compatible with leishmaniasis were observed in any species other than the dogs. Although the dog is probably the primary reservoir of leishmaniasis in endemic areas, the prevalence and the absence of apparent signs of this disease within the island's abundant feral cat and pine marten populations could make these species potential primary or secondary hosts of L. infantum in Mallorca.