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Le Touquet – Paris-Plage, France

Bertrand M.,French Institute of Health and Medical Research | Bertrand M.,University Paris - Sud | Petit V.,Institute Curie | Petit V.,French Institute of Health and Medical Research | And 15 more authors.
Cell Cycle | Year: 2015

The epithelial to mesenchymal transition (EMT) is an essential process during development and during tumor progression. Here, we observed the accumulation of the selective autophagy receptor and signaling adaptor sequestosome-1 (SQSTM1/p62) during growth factor-induced EMT in immortalized and tumor-derived epithelial cell lines. Modulation of the p62 level regulated the expression of junctional proteins. This effect was dependent on the ubiquitin-associated domain of p62, which stabilized the TGFb/Smad signaling co-activator Smad4 and the EMT transcription factor Twist. This study highlights a novel function of p62 in a major epithelial phenotypic alteration. © 2015 Taylor & Francis Group, LLC.

Galluzzi L.,French Institute of Health and Medical Research | Galluzzi L.,University of Paris Descartes | Pietrocola F.,French Institute of Health and Medical Research | Bravo-San Pedro J.M.,French Institute of Health and Medical Research | And 28 more authors.
EMBO Journal | Year: 2015

Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy. Autophagy has been described to have tumor-suppressive as well as tumor-promoting functions. This review discusses how stage and context alters the role for autophagy in cancer, and argues for further research prior to targeting autophagy in cancer therapy. © 2015 The Authors.

Hammerschmidt K.,German Primate Center | Schreiweis C.,Institute Necker Enfants Malades INEM | Minge C.,German Primate Center | Paabo S.,Max Planck Institute for Evolutionary Anthropology | And 2 more authors.
Genes, Brain and Behavior | Year: 2015

The transcription factor FOXP2 has been linked to severe speech and language impairments in humans. An analysis of the evolution of the FOXP2 gene has identified two amino acid substitutions that became fixed after the split of the human and chimpanzee lineages. Studying the functional consequences of these two substitutions in the endogenous Foxp2 gene of mice showed alterations in dopamine levels, striatal synaptic plasticity, neuronal morphology and cortico-striatal-dependent learning. In addition, ultrasonic vocalizations (USVs) of pups had a significantly lower average pitch than control littermates. To which degree adult USVs would be affected in mice carrying the 'humanized' Foxp2 variant remained unclear. In this study, we analyzed USVs of 68 adult male mice uttered during repeated courtship encounters with different females. Mice carrying the Foxp2hum/hum allele did not differ significantly in the number of call elements, their element structure or in their element composition from control littermates. We conclude that neither the structure nor the usage of USVs in adult mice is affected by the two amino acid substitutions that occurred in FOXP2 during human evolution. The reported effect for pup vocalization thus appears to be transient. These results are in line with accumulating evidence that mouse USVs are hardly influenced by vocal learning. Hence, the function and evolution of genes that are necessary, but not sufficient for vocal learning in humans, must be either studied at a different phenotypic level in mice or in other organisms. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Chamouni A.,Institute Necker Enfants Malades INEM | Chamouni A.,French Institute of Health and Medical Research | Chamouni A.,University of Paris Descartes | Schreiweis C.,Institute Necker Enfants Malades INEM | And 5 more authors.
Reviews in Endocrine and Metabolic Disorders | Year: 2015

In the past 15 years, the field of physiology has been radically challenged by landmark studies using novel tools of genetic engineering. Particular to our interest, the reciprocal interactions between the skeleton and the nervous system were shown to be major ones. The demonstration that brain, via multiple pathways, is a powerful regulator of bone growth, has shed light on an important central regulation of skeletal homeostasis. More recently, it was shown that bone might return the favor to the brain through the secretion of a bone-derived hormone, osteocalcin. The skeleton influences development and cognitive functions of the central nervous system at different stages throughout life suggesting an intimate dialogue between bone and brain. © 2015, Springer Science+Business Media New York.

Orhon I.,French Institute of Health and Medical Research | Orhon I.,Institute Necker Enfants Malades INEM | Orhon I.,University of Paris Descartes | Dupont N.,French Institute of Health and Medical Research | And 7 more authors.
Cell Death and Differentiation | Year: 2015

Motile and primary cilia (PC) are microtubule-based structures located at the cell surface of many cell types. Cilia govern cellular functions ranging from motility to integration of mechanical and chemical signaling from the environment. Recent studies highlight the interplay between cilia and autophagy, a conserved cellular process responsible for intracellular degradation. Signaling from the PC recruits the autophagic machinery to trigger autophagosome formation. Conversely, autophagy regulates ciliogenesis by controlling the levels of ciliary proteins. The cross talk between autophagy and ciliated structures is a novel aspect of cell biology with major implications in development, physiology and human pathologies related to defects in cilium function. © 2015 Macmillan Publishers Limited All rights reserved.

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