Extracellular vesicles released by non-small cell lung cancer cells drive invasion and permeability in non-tumorigenic lung epithelial cells.

Extracellular vesicles (EVs) released from non-small cell lung cancer (NSCLC) cells are known to promote cancer progression. However, it remains unclear how EVs from various NSCLC cells differ in their secretion profile and their ability to promote phenotypic changes in non-tumorigenic cells. Here, we performed a comparative analysis of EV release from non-tumorigenic cells (HBEC/BEAS-2B) and several NSCLC cell lines (A549, H460, H358, SKMES, and Calu6) and evaluated the potential impact of NSCLC EVs, including EV-encapsulated RNA (EV-RNA), in driving invasion and epithelial barrier impairment in HBEC/BEAS-2B cells.

Silencing Mist1 Gene Expression Is Essential for Recovery from Acute Pancreatitis.

Acinar cells of the exocrine pancreas are tasked with synthesizing, packaging and secreting vast quantities of pro-digestive enzymes to maintain proper metabolic homeostasis for the organism. Because the synthesis of high levels of hydrolases is potentially dangerous, the pancreas is prone to acute pancreatitis (AP), a disease that targets acinar cells, leading to acinar-ductal metaplasia (ADM), inflammation and fibrosis-events that can transition into the earliest stages of pancreatic ductal adenocarcinoma. Despite a wealth of information concerning the broad phenotype associated with pancreatitis, little is understood regarding specific transcriptional regulatory networks that are susceptible to AP and the role these networks play in acinar cell and exocrine pancreas responses.

RNA-guided CRISPR-Cas technologies for genome-scale investigation of disease processes.

From its discovery as an adaptive bacterial and archaea immune system, the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system has quickly been developed into a powerful and groundbreaking programmable nuclease technology for the global and precise editing of the genome in cells. This system allows for comprehensive unbiased functional studies and is already advancing the field by revealing genes that have previously unknown roles in disease processes. In this review, we examine and compare recently developed CRISPR-Cas platforms for global genome editing and examine the advancements these platforms have made in guide RNA design, guide RNA/Cas9 interaction, on-target specificity, and target sequence selection.

Extensive pancreas regeneration following acinar-specific disruption of Xbp1 in mice.

Background & Aims: Progression of diseases of the exocrine pancreas, which include pancreatitis and cancer, is associated with increased levels of cell stress. Pancreatic acinar cells are involved in development of these diseases and, because of their high level of protein output, they require an efficient, unfolded protein response (UPR) that mediates recovery from endoplasmic reticulum (ER) stress following the accumulation of misfolded proteins.

Methods: To study recovery from ER stress in the exocrine organ, we generated mice with conditional disruption of Xbp1 (a principal component of the UPR) in most adult pancreatic acinar cells (Xbp1fl/fl).

Batf promotes growth arrest and terminal differentiation of mouse myeloid leukemia cells.

Batf is a basic leucine zipper transcription factor belonging to the activator protein-1 superfamily. Batf expression is regulated following stimulation of both lymphoid and myeloid cells. When treated with leukemia inhibitory factor, mouse M1 myeloid leukemia cells commit to a macrophage differentiation program that is dependent on Stat3 and involves the induction of Batf gene transcription via the binding of Stat3 to the Batf promoter.

EBNA2 and activated Notch induce expression of BATF.

The immortalization of human B lymphocytes by Epstein-Barr virus (EBV) requires the virus-encoded transactivator EBNA2 and the products of both viral and cellular genes which serve as EBNA2 targets. In this study, we identified BATF as a cellular gene that is up-regulated dramatically within 24 h following the infection of established and primary human B cells with EBV. The transactivation of BATF is mediated by EBNA2 in a B-cell-specific manner and is duplicated in non-EBV-infected B cells by the expression of mammalian Notch proteins.

Stat3-dependent induction of BATF in M1 mouse myeloid leukemia cells.

Stat3 mediates cellular responses associated with proliferation, survival and differentiation, but the mechanisms underlying the diverse effects of this signaling molecule remain unknown. M1 mouse myeloid leukemia cells arrest growth and differentiate into macrophages following treatment with interleukin 6 (IL-6) or leukemia inhibitory factor (LIF), and recent studies have shown that Stat3 plays a central role in this process. Utilizing representational difference analysis, we demonstrate that expression of the mouse BATF gene is upregulated as an early response to IL-6/LIF stimulation and Stat3 activation in this cell system.