Pancreatic Cell News Volume 6.09 | Mar 10 2015

Loss of Egr-1 Sensitizes Pancreatic β-Cells to Palmitate-Induced ER Stress and Apoptosis
To understand how β-cells sense fatty acid stimuli and translate into a long-term adaptive response, scientists investigated whether palmitic acid regulates early growth response-1, an immediate-early transcription factor, which is induced by many environmental stimuli and implicated in cell proliferation, differentiation, and apoptosis. [J Mol Med] Abstract

Photoactivation of Akt1/GSK3β Isoform-Specific Signaling Axis Promotes Pancreatic β-Cell Regeneration
Researchers showed that low-power laser irradiation (LPLI) promoted β-cell replication and cell cycle progression through activation of Akt1/GSK3β isoform-specific signaling axis. Inhibition of PI3-K/Akt or GSK3 with specific inhibitors dramatically reduced or increased LPLI-induced β-cell replication, revealing Akt/GSK3 signaling axis was involved in β-cell replication and survival upon LPLI treatment. [J Cell Biochem] Abstract

HAP1 Helps to Regulate Actin-Based Transport of Insulin-Containing Granules in Pancreatic β Cells
Scientists used time-lapse laser scanning confocal microscopy to provide direct evidence that huntingtin-associated protein 1 (HAP1)A, but not HAP1B, co-localizes and co-migrates with insulin-containing vesicles and actin-based myosin Va motor protein in the INS-1 pancreatic β cell line. [Histochem Cell Biol] Abstract

PANCREATIC CANCER

ERK Kinase Phosphorylates and Destabilizes the Tumor Suppressor FBW7 in Pancreatic Cancer
Researchers showed that ERK directly interacted with F-box and WD repeat domain-containing 7 (FBW7) and phosphorylated FBW7 at Thr205, which sequentially promoted FBW7 ubiquitination and proteasomal degradation. Furthermore, the phospho-deficient T205A FBW7 mutant is resistant to ERK activation and could significantly suppress pancreatic cancer cell proliferation and tumorigenesis. [Cell Res] Full Article

(Pro)Renin Receptor Is Crucial for Wnt/β-Catenin-Dependent Genesis of Pancreatic Ductal Adenocarcinoma
Scientists identified aberrant expression of (pro)renin receptor ((P)RR) in premalignant PanIN and pancreatic ductal adenocarcinoma (PDAC) lesions and all the PDAC cell lines examined. Inhibiting (P)RR with an siRNA attenuated activation of Wnt/β-catenin signaling pathway and reduced the proliferative ability of PDAC cells in vitro and the growth of engrafted tumors in vivo. [Sci Rep] Full Article

miR-186 and 326 Predict the Prognosis of Pancreatic Ductal Adenocarcinoma and Affect the Proliferation and Migration of Cancer Cells
Researchers correlated the expression of 36 potentially prognostic miRNAs within pancreatic ductal adenocarcinoma (PDAC) tissue with clinico-pathological features and survival in 151 Chinese patients. They then analyzed the functional roles and target genes of two miRNAs in PDAC development. [PLoS One]
Full Article

Longikaurin E Induces Apoptosis of Pancreatic Cancer Cells via Modulation of the p38 and PI3K/AKT Pathways by ROS
Pancreatic cancer cell lines cultured in the presence of longikaurin E exhibited dose- and time-dependent growth suppression by clone formation, methylthiazoltetrazolium assay, lactate dehydrogenase cytotoxicity assay, and fluorescence-activated cell sorting analysis, respectively. [Naunyn Schmiedebergs Arch Pharmacol] Abstract

Efficacy of Irreversible Electroporation in Human Pancreatic Adenocarcinoma: Advanced Murine Model
Scientists hypothesized that incomplete ablation leads to early recurrence and a more aggressive biology. They created the first ever heterotopic murine model by inoculating BALB/c nude mice in the hindlimb with a subcutaneous injection of Panc-1 cells, an immortalized human pancreatic adenocarcinoma cell line. [Mol Ther Methods Clin Dev] Full Article

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Medimmune and Joslin Diabetes Center Announce New Research Collaboration Focused on Advancing Metabolic Disease Research
MedImmune and Joslin Diabetes Center announced a three-year research collaboration to develop new medicines for the treatment of diabetes, obesity, and related metabolic disorders. [Joslin Diabetes Center] Press Release

Targovax to Expand Ongoing Phase I/II CT-TG01-01 Pancreatic Cancer Study with a New Group of Up to 13 Patients
Targovax’s lead compound TG01, a novel peptide vaccine against cancer specific RAS mutations, is currently being tested in a Phase I/II study in combination with gemcitabine as an adjuvant treatment in resected pancreatic cancer. The purpose of the trial expansion is to build on the positive findings of immune responses to further optimize the TG01 treatment regimen and safety profile of the combination therapy. [Targovax (Business Wire)] Press Release

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Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

PhD Student Positions – Regenerative Medicine/Stem Cell Biology (University Hospital Tubingen)

Tenure-Track Immunology Faculty Position – Diabetes (University of Connecticut Health Center)

Clinical Research Fellow – Pancreatic Cancer Biology (Cancer Research UK)

Postdoctoral Position – Endothelial Dysfunction and Diabetes (Weill Cornell Medical College in Qatar)

Director – Vector Production (Sangamo BioSciences, Inc.)

Senior Process Development Engineer (Sangamo BioSciences, Inc.)

Assistant/Associate Professor – Endocrinology, Diabetes and Metabolism Research (University of Pennsylvania)

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