Pancreatic Cell News Volume 10.40 | Oct 15 2019

TOP STORY

The Long Noncoding RNA Paupar Modulates PAX6 Regulatory Activities to Promote Alpha Cell Development and Function

Comparative transcriptome analyses between embryonic mouse pancreas and adult mouse islets identified several pancreatic lncRNAs that lay in close proximity to essential pancreatic transcription factors, including the Pax6-associated lncRNA Paupar. Investigators demonstrated that Paupar was enriched in glucagon-producing α cells where it promoted the alternative splicing of Pax6 to an isoform required for activation of essential α cell genes. [Cell Metab] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Sufu– and Spop-Mediated Downregulation of Hedgehog Signaling Promotes Beta Cell Differentiation through Organ-Specific Niche Signals

To define organ-specific niche signals, researchers isolated pancreatic and gastrointestinal stromal cells, and analyzed their gene expression during development. Genetic studies revealed the importance of tightly regulated Hedgehog signaling in the pancreatic mesenchyme: inactivation of mesenchymal signaling led to annular pancreas, whereas stroma-specific activation of signaling via loss of Hedgehog regulators, Sufu and Spop, impaired pancreatic growth and beta cell genesis. [Nat Commun] Full Article

Expression Levels of Enzymes Generating NO and CO in Islets of Murine and Human Diabetes

Plasma glucose and plasma insulin were recorded and β-cell expression levels of the different enzymes were measured with confocal microscopy and fluorescence intensity recordings. In human islets taken from nondiabetic controls and type 2 diabetes the expression of the enzymes was analyzed by RNA-sequencing and qPCR. [Biochem Biophys Res Commun] Abstract

PANCREATIC CANCER

Targeting TGFβR2-Mutant Tumors Exposes Vulnerabilities to Stromal TGFβ Blockade in Pancreatic Cancer

Scientists demonstrated that inhibition of stromal TGFβR2 reduced IL-6 production from cancer-associated fibroblasts, resulting in a reduction of STAT3 activation in tumor cells and reversion of the immunosuppressive landscape. Up to 7% of human pancreatic ductal adenocarcinoma had tumor cell-specific deficiency in canonical TGFβ signaling via loss of TGFβR2. [EMBO Mol Med] Full Article | Graphical Abstract

NO^•/RUNX3/Kynurenine Metabolic Signaling Enhances Disease Aggressiveness in Pancreatic Cancer

Kynurenine treatment enhanced spheroid growth and invasive potential of pancreatic cancer cell lines. Mechanistically, NO^•-induced IDO1/Kynurenine/AHR signaling was mediated by RUNX3 transcription factor. [Int J Cancer] Abstract

KAT2A Succinyltransferase Activity-Mediated 14-3-3ζ Upregulation Promotes β-Catenin Stabilization-Dependent Glycolysis and Proliferation of Pancreatic Carcinoma Cells

Expression of succinyltransferase activity-defective KAT2A Y645A reduced H3K79 succinylation and 14-3-3ζ expression, leading to decreased β-catenin stability and subsequently decreased expression of cyclin D1, c-Myc, GLUT1, and LDHA. KAT2A-mediated 14-3-3ζ and β-catenin expression promoted glycolysis, cell proliferation, and migration and invasion of pancreatic ductal adenocarcinoma cells with epithelial-to-mesenchymal transition. [Cancer Lett] Abstract

LINC01559 Accelerates Pancreatic Cancer Cell Proliferation and Migration through YAP-Mediated Pathway

Scientists showed that LINC01559 was stimulated in pancreatic cancer (PC) cell lines relative to normal controls. They validated that LINC01559 facilitated PC cell proliferation and migration in vitro. [J Cell Physiol] Abstract

Impact of CD36 on Chemoresistance in Pancreatic Ductal Adenocarcinoma

CD36 expression was assessed in pancreatic ductal adenocarcinoma cell lines (PDAC). Gemcitabine-resistant PDAC cell lines were transfected with small interfering RNA that specifically targeted CD36 to evaluate chemoresistance and apoptosis. [Ann Surg Oncol] Abstract

The Effect of Resveratrol and Quercetin on Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem Cell

Cancer stem cells were obtained from the PANC-1 cells by the MiniMACS system. CD133⁺ and CD133^– PANC-1 cells were treated with different concentrations of resveratrol and quercetin. Cell growth and cytotoxicity were evaluated by MTT assay. [Nutr Cancer] Abstract

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GATA Factors in Pancreas Development and Disease

Recent studies have revealed that GATA transcription factors are involved in various stages of pancreas formation and in the adult β cell function. The authors review the fundamental role of GATA transcription factors in pancreas morphogenesis and their association with congenital diseases associated with pancreas. [IUBMB Life] Abstract

Pancreatic β Cells Express MHC Class II： Do Diabetic β Cells Have the Capacity of Antigen-Presenting Cells?

Genetic factors, environmental factors, and autoimmunity contribute to pancreatic β cell destruction in type 1 diabetes. As genetic factors, MHC class II gene polymorphisms have been shown to contribute most strongly to susceptibility to type 1 diabetes, and disease susceptibility haplotypes for each race have also been identified. [J Diabetes Investig] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.

$1.5M Grant to Physics Professor Bolsters Cancer-Centered Research at UTEP

The Department of Physics at The University of Texas at El Paso (UTEP) was recently awarded a $1.5 million grant to research kinesins as potential targets for cancer drug development. Lin Li, PhD, assistant professor of computational biophysics, is the sole principal investigator of the four-year study, which will investigate important mechanisms for kinesins, a type of biological motor protein. [El Paso Herald-Post] Press Release

New UW Center Receives NIH Grant to Improve the Fight against Cancer

To bridge the gap between cancer interventions and their implementation within communities across the United States, the National Institute of Health’s National Cancer Institute is funding the creation of six implementation science centers focused on cancer control. [The University of Washington] Press Release

Hundreds of Scientists Declare Support for Extinction Rebellion

Almost 1,000 scientists have signed a declaration supporting civil disobedience protests that urge government action on climate change. [The Scientist] Editorial

Thousands of Grant Peer Reviewers Share Concerns in Global Survey

Researchers spend around ten days every year reviewing other academics’ funding proposals, according to the largest ever survey of grant peer review. The Grant Review In Focus report — based on a survey of 4,700 researchers worldwide — also found that recognition is an important incentive for reviewers. [Nature News] Editorial

Canadian Election Leaves Scientists Hanging — No Matter Who Wins

Canada’s two main political parties are running neck and neck in the lead-up to the country’s general election on 21 October. It’s unclear which party will come out on top, and that uncertainty extends to how science will fare in the next government. [Nature News] Editorial

NEW Tumor Immunology and Immunotherapy
November 17-20, 2019
Boston, Massachusetts, United States

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NEW Research Associate – Human Organogenesis (The University of Manchester)

Postdoctoral Researcher – Metabolic Regulation and Diabetes (City of Hope)

Group Leader – Diabetes Research (International Centre for Genetic Engineering and Biotechnology)

Faculty Position – Cancer Biology (Children’s Research Institute at UT Southwestern)

Postdoctoral Fellow – Pancreatic Cancer (The University of Alabama at Birmingham)

Postdoctoral Position – Pancreatic Ductal Adenocarcinoma (IT University of Copenhagen)

Research Technition – Diabetes, Allergies, and Lung Diseases (Helmholtz Zentrum München)

Postdoctoral Researcher – Endocrinology, Diabetes, and Metabolism (The University of Alabama at Birmingham)

Postdoctoral Fellowship – Regenerative Medicine and Metabolic Biology (Indiana Biosciences Research Institute)

Research Positions – Pancreatic Beta-Cells (Université de Montréal)

Postdoctoral Fellow – Neuroscience and Diabetes (The Child Health Institute of New Jersey)

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