The proto-oncogene encodes a pivotal tyrosine kinase receptor, binding the hepatocyte growth factor (HGF, also known as scatter factor, SF) and governing essential biological processes such as organogenesis, tissue repair, and angiogenesis. The pleiotropic physiological functions of MET explain its diverse role in cancer progression in a broad range of tumors; genetic/epigenetic alterations of drive tumor cell dissemination, metastasis, and acquired resistance to conventional and targeted therapies. Therefore, targeting MET emerged as a promising strategy, and many efforts were devoted to identifying the optimal way of hampering MET signaling.
View Article and Find Full Text PDFAdipose tissue macrophages (ATMs) play an important role in obesity and inflammation, and they accumulate in adipose tissue (AT) with aging. Furthermore, increased ATM senescence has been shown in obesity-related AT remodeling and dysfunction. However, ATM senescence and its role are unclear in age-related AT dysfunction.
View Article and Find Full Text PDFis an oncogene encoding the tyrosine kinase receptor for hepatocyte growth factor (HGF). Upon ligand binding, MET activates multiple signal transducers, including PI3K/AKT, STAT3, and MAPK. When mutated or amplified, becomes a "driver" for the onset and progression of cancer.
View Article and Find Full Text PDFA significant challenge of functional genomics is to develop methods for genome-scale acquisition and analysis of cell biological data. Here, we present an integrated method that combines genome-wide genetic perturbation of Saccharomyces cerevisiae with high-content screening to facilitate the genetic description of sub-cellular structures and compartment morphology. As proof of principle, we used a Rad52-GFP marker to examine DNA damage foci in ∼20 million single cells from ∼5,000 different mutant backgrounds in the context of selected genetic or chemical perturbations.
View Article and Find Full Text PDFThe Rif1 protein, originally identified as a telomere-binding factor in yeast, has recently been implicated in DNA replication control from yeast to metazoans. Here, we show that budding yeast Rif1 protein inhibits activation of prereplication complexes (pre-RCs). This inhibitory function requires two N-terminal motifs, RVxF and SILK, associated with recruitment of PP1 phosphatase (Glc7).
View Article and Find Full Text PDFBackground: Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer.
Methods: ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR.