Regulation of a progenitor gene program by SOX4 is essential for mammary tumor proliferation

In breast cancer the transcription factor SOX4 has been shown to be associated with poor survival, increased tumor size and metastasis formation. This has mostly been attributed to the ability of SOX4 to regulate Epithelial-to-Mesenchymal-Transition (EMT). However, SOX4 regulates target gene transcription in a context-dependent manner that is determined by the cellular and epigenetic state. In this study we have investigated the loss of SOX4 in mammary tumor development utilizing organoids derived from a PyMT genetic mouse model of breast cancer. Using CRISPR/Cas9 to abrogate SOX4 expression, we found that SOX4 is required for inhibiting differentiation by regulating a subset of genes that are highly activated in fetal mammary stem cells (fMaSC). In this way, SOX4 re-activates an oncogenic transcriptional program that is regulated in many progenitor cell-types during embryonic development. SOX4-knockout organoids are characterized by the presence of more differentiated cells that exhibit luminal or basal gene expression patterns, but lower expression of cell cycle genes. In agreement, primary tumor growth and metastatic outgrowth in the lungs are impaired in SOX4KO tumors. Finally, SOX4KO tumors show a severe loss in competitive capacity to grow out compared to SOX4-proficient cells in primary tumors. Our study identifies a novel role for SOX4 in maintaining mammary tumors in an undifferentiated and proliferative state. Therapeutic manipulation of SOX4 function could provide a novel strategy for cancer differentiation therapy, which would promote differentiation and inhibit cycling of tumor cells

Ricerca e sviluppo di nuovi probiotici. Impieghi attuali e futuri

Impieghi attuali e futuri nella ricerca e sviluppo di nuovi probiotici

Monte-Carlo simulation of decananometric nMOSFETs: Multi-subband vs. 3D-electron gas with quantum corrections

In this paper two Monte-Carlo simulators implementing different models for the influence of carrier quantization on the electrostatics and transport are used to analyze sub-100 nm double-gate SOI devices. To this purpose a new stable and efficient scheme to implement the contacts in the simulation of double-gate SOI devices is introduced first. Then, results in terms of drain current and microscopic quantities are compared, providing new insight on the limitation of a well assessed semiclassical transport simulation approach and a more rigorous multi-subband model

Comparison of Monte Carlo Transport Models for Nanometer-Size MOSFETs

This paper presents the results of a comparison among five Monte Carlo device simulators for nano-scale MOSFETs. These models are applied to the simulation of the I-V characteristics of a 25 nm gate-length MOSFET representative of the high-performance transistor of the 65 nm technology node. Appreciable differences between the simulators are obtained in terms of simulated ION. These differences are mainly related to different treatments of the ionized impurity scattering (IIS) and pinpoint a limitation of the available models for screening effects at very large carrier concentrations