DIABETES & PANCREATITIS Peroxiredoxin 4 Improves Insulin Biosynthesis and Glucose-Induced Insulin Secretion in Insulin-Secreting INS-1E Cells Researchers examined the functional significance of peroxiredoxin 4 (Prdx4) on β-cell function with emphasis on insulin content and secretion during stimulation with nutrient secretagogues. Overexpression of Prdx4 in glucose-responsive insulin-secreting INS-1E cells significantly metabolized luminal hydrogen peroxide and improved the glucose-induced insulin secretion which was accompanied by the enhanced proinsulin mRNA transcription and insulin content. [J Biol Chem] Abstract | Full Article Retinoic Acid Plays an Evolutionarily Conserved and Biphasic Role in Pancreas Development Researchers produced a transgenic retinoic acid (RA) reporter, which demonstrated that pancreatic Notch-responsive cells directly respond to RA signaling through the canonical transcriptional pathway. Next, using a genetic lineage tracing approach, they demonstrated these progenitors produce endocrine cells following inhibition of RA signaling. [Dev Biol] Abstract MafA Is Required for Postnatal Proliferation of Pancreatic β-Cells Maturation of β-cells is accompanied by increased expression of MafA, an insulin gene transcription factor. Transcriptome analysis of MafA knockout islets revealed MafA is required for the expression of several molecules critical for β-cell function, including Glut2, ZnT8, Granuphilin, Vdr, Pcsk1 and Urocortin 3, as well as Prolactin receptor and its downstream target Cyclin D2. [PLoS One] Full Article Involvement of RhoA/ROCK in Insulin Secretion of Pancreatic β-Cells in 3D Culture Mouse insulinoma 6 (MIN6) cells were cultured in a rotating three-dimensional (3D) culture system to form islet-like aggregates. In the 3D-cultured MIN6 cells, more endocrine-specific genes were up-regulated, and glucose-stimulated insulin secretion was increased to a greater extent than in cells grown in monolayers. [Cell Tissue Res] Abstract PANCREATIC CANCER Nicotine Promotes Initiation and Progression of KRAS-Induced Pancreatic Cancer via Gata6-Dependent Dedifferentiation of Acinar Cells in Mice Administration of nicotine accelerated transformation of pancreatic cells and tumor formation in RASG12V and KPC mice. Nicotine induced dedifferentiation of acinar cells by activating AKT-ERK-MYC signaling; this led to inhibition of Gata6 promoter activity, loss of GATA6 protein, and subsequent loss of acinar differentiation and hyperactivation of oncogenic KRAS. [Gastroenterology] Abstract Dual Targeting of ErbB-2/ErbB-3 Results in Enhanced Antitumor Activity in Preclinical Models of Pancreatic Cancer Researchers report that despite epidermal growth factor (EGF) receptor overexpression, pancreatic cancer cells are more sensitive to NRG-1β than EGF in terms of Akt activation and cell proliferation. [Oncogenesis] Full Article Inhibition of Endoglin-GIPC Interaction Inhibits Pancreatic Cancer Cell Growth Investigators evaluated the effects of targeting endoglin in pancreatic cancer both in vitro and in vivo. They analyzed the anti-proliferative effect of both RNAi-based and peptide ligand-based inhibition of endoglin in pancreatic cancer cell lines, the latter yielding a GAIP-interacting protein, C terminus (GIPC) PDZ domain-targeting lipopeptide with notable anti-proliferative activity. [Mol Cancer Ther] Abstract Embelin Inhibits Pancreatic Cancer Progression by Directly Inducing Cancer Cell Apoptosis and Indirectly Restricting IL-6 Associated Inflammatory and Immune Suppress Cells The anti-inflammation and anti-tumor effects of embelin on pancreatic cancer were investigated. Embelin significantly attenuated cells invasion, proliferation and induced apoptosis by down-regulating STAT3 and up-regulating p53 signaling pathways in vitro. [Cancer Lett] Abstract The Actin-Bundling Protein TRIOBP-4 and -5 Promotes the Motility of Pancreatic Cancer Cells Researchers show that TRIOBP isoforms 4 and 5 (TRIOBP-4/-5) was up-regulated in human pancreatic carcinoma cells. Knockdown of TRIOBP-4/-5 led to a loss of filopodia and a decrease in cell motility. [Cancer Lett] Abstract MicroRNA-1246 Expression Associated with CCNG2-Mediated Chemoresistance and Stemness in Pancreatic Cancer The in vitro drug sensitivity of pancreatic cancer cells was altered according to the microRNA (miR)-1246 expression via CCNG2. In vivo, scientists found that miR-1246 could increase tumor-initiating potential and induced drug resistance. [Br J Cancer] Abstract |