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Angela Nieto’s team has been working for 14 years in the functional analysis of the Snail gene family. After spending several years at the National Institute for Medical Research, London, Nieto is now a research professor at the Institute of Neurosciences of Alicante, where he heads a research group devoted to motion analysis and cellular plasticity. The first results of the group pointed to a fundamental role of Snail genes in embryonic smooth .
In this work, published in The EMBO Journal, Nieto group presents, in collaboration with the Hospital de San Juan de Alicante and the Imperial College of London, the first data that could result in the use of control of the expression of Snail as a diagnostic marker and target for anticancer therapies.
During embryonic development, the kidney epithelium originates from mesenchymal cells, whereas the opposite regression process has been associated with epithelial tumors and fibrosis leading to renal failure. It is known that Snail participates in the progression of such tumors, but so far no known role in development. This study has allowed recognition of Snail genes as a group of lowered expression during development and that this inhibition is correlated with the expression of cadherin-16. By contrast, Snail-induced activation leads to suppression of cadherin-16 through renal differentiation factors, which marked a new path of impaired kidney homeostasis. In turn, activation induces renal fibrosis in transgenic mice, while normal Snail expression remains silent.
In this work, directed by Dr. Angela Nieto of the Instituto de Neurociencias de Alicante, it becomes evident that the first Snail1 transcriptional repressor of Runx2, which controls the activity of this protein complex during differentiation of osteoblasts.
The bones are undergoing a process of constant remodeling throughout life, being the balance between its formation by osteoblasts and resorption by osteoclasts that determines bone mass. Read the rest of this entry »
The fate of a cell is determined by signals from their environment and their ability to respond to them. Some signaling pathways are involved in vital decisions during the development of organisms, this being an example of epithelial-mesenchymal transition (EMT), a transformation of epithelial cells into mesenchymal cells with migratory and invasive capacity in developing normal (in fact, crucial for the formation of different embryonic tissues, notably the mesoderm and neural crest), but also occurs in pathological conditions such as tumor progression in aggressive carcinomas. Read the rest of this entry »
Snail is a transcription factor that controls epithelial-mesenchymal transitions, processes also involved in the metastasis of epithelial tumors. This control is exercised by repressing expression of E-cadherin, and other epithelial genes.
The work done by the research group of Dr. Portillo is a step forward in understanding the mechanisms that regulate the function of Snail.
It shows that the enzymes lysyl oxidase 2 and 3 (LOXL2 and LOXL3) interact and cooperate in infraexpresion of E-cadherin mediated by this transcription factor. Snail has two lysine, Lys98 and 137, very important for stability, for their cooperation with the lysyl oxidase and, ultimately, for their role in controlling epithelial-mesenchymal transitions. Read the rest of this entry »