Pancreatic Cell News Volume 10.31 | Aug 13 2019

TOP STORY

Mutations in RABL3 Alter KRAS Prenylation and Are Associated with Hereditary Pancreatic Cancer

Transcriptomic and mass spectrometry approaches implicated RAS oncogene family-like 3 (RABL3) in RAS pathway regulation and identified an interaction with RAP1GDS1, a chaperone regulating prenylation of RAS GTPases3. The truncated mutant RABL3 protein accelerated KRAS prenylation and required RAS proteins to promote cell proliferation. [Nat Genet] Abstract | Press Release

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Modeling Monogenic Diabetes Using Human ESCs Reveals Developmental and Metabolic Deficiencies Caused by Mutations in HNF1A

Researchers used genome edited human embryonic stem cells to understand the most common form of monogenic diabetes, MODY3, caused by mutations in the transcription factor HNF1A. They found that HNF1A was necessary to repress an alpha cell gene expression signature, maintain endocrine cell function, and regulate cellular metabolism. [Cell Stem Cell] Abstract | Graphical Abstract

PAHSAs Attenuate Immune Responses and Promote β Cell Survival in Autoimmune Diabetic Mice

Palmitic acid esters of hydroxy stearic acids (PAHSAs) promoted β cell proliferation in both nonobese diabetic (NOD) mice and MIN6 cells and increased the number of β cells in NOD mice. PAHSAs attenuated cytokine-induced apoptotic and necrotic β cell death and increased β cell viability. [J Clin Invest] Full Article

PANCREATIC CANCER

Comprehensive Transcriptomic Analysis of Cell Lines as Models of Primary Tumors across 22 Tumor Types

Investigators present pancreatic cancer results as a case study and find that the commonly used cell line MIA PaCa-2 was transcriptionally unrepresentative of primary pancreatic adenocarcinomas. They proposed a new cell line panel, the TCGA-110-CL, for pan-cancer studies. [Nat Commun] Full Article

CAF Hierarchy Driven by Pancreatic Cancer Cell p53-Status Creates a Pro-Metastatic and Chemoresistant Environment via Perlecan

The authors revealed the existence of a p53-driven hierarchy, where cancer cells with a gain-of-function (GOF) mutant p53 educated a dominant population of cancer-associated fibroblasts (CAFs) that established a pro-metastatic environment for GOF and null p53 cancer cells alike. They also demonstrated that CAFs educated by null p53 cancer cells could be reprogrammed by either GOF mutant p53 cells or their CAFs. [Nat Commun] Abstract | Press Release

PORCN Inhibition Synergizes with PI3K/mTOR Inhibition in Wnt-Addicted Cancers

Multiple PI3K/mTOR pathway inhibitors in combination with ETC-159 synergistically suppressed the growth of multiple Wnt-addicted cancer cell lines in soft agar. Furthermore, the combination of the PORCN inhibitor ETC-159 and the pan-PI3K inhibitor GDC-0941 potently suppressed the in vivo growth of RNF43-mutant pancreatic cancer xenografts. [Oncogene] Full Article

LINC00346 Promotes Pancreatic Cancer Progression through the CTCF-Mediated Myc Transcription

Researchers showed that LINC00346 was highly expressed in pancreatic tumor specimens as compared to normal pancreatic tissue based on interrogation of The Cancer Genome Atlas pancreatic adenocarcinoma dataset. Of significance, this upregulation of LINC00346 was associated with overall survival and disease-free survival, respectively. [Oncogene] Abstract

PUM1 Knockdown Prevents Tumor Progression by Activating the PERK/eIF2/ATF4 Signaling Pathway in Pancreatic Adenocarcinoma Cells

Investigators found that the PUM1 protein levels were higher in pancreatic ductal adenocarcinoma (PDAC) tissues than in adjacent tissues and that PUM1 levels were significantly associated with TNM stage and overall survival time, indicating a correlation between high PUM1 expression and poor prognosis in patients with PDAC. [Cell Death Dis] Full Article

Pancreatic (Pro)enzymes Treatment Suppresses BXPC-3 Pancreatic Cancer Stem Cell Subpopulation and Impairs Tumor Engrafting

The authors investigated in vitro and in vivo the effects of a pancreatic (pro)enzyme mixture composed of chymotrypsinogen and trypsinogen (PRP) on cancer stem cells (CSCs) derived from a human pancreatic cell line, BxPC3. Exposure of pancreatic CSCs spheres to PRP resulted in a significant decrease of ALDEFLUOR and specific pancreatic CSC markers signal tested by flow cytometry, further CSCs markers expression was also analyzed by western and immunofluorescence assays. [Sci Rep] Full Article

Protective Effect of Nobiletin on Isolated Human Islets Survival and Function against Hypoxia and Oxidative Stress-Induced Apoptosis

Scientists evaluated the effect of nobiletin on the cultured human islets. Isolated human islets were treated by different concentrations of nobiletin and cultured for 24 and 72 hours. Then, the islets viability, apoptosis, insulin and C-peptide secretion, and apoptosis markers were evaluated. [Sci Rep] Full Article

Subscribe to one of our other 19 science newsletters such as Hepatic Cell News & Intestinal Cell News.

Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes

Dedifferentiation is well characterized by the decrease in expression of key β cell markers such as genes encoding major transcription factors and an increase in atypical or “disallowed” genes for β cells such as lactate dehydrogenase, monocarboxylate transporter MCT1, or progenitor cell genes. Moreover, altered identity of mature β cells in diabetes also involves transdifferentiation of β cells into other islet hormone producing cells. [Curr Diab Rep] Abstract

The Beta Cell in Type 2 Diabetes

In the setting of type 2 diabetes, β-cells undergo changes in gene expression, reverting to a more immature state and in some cases transdifferentiating into other islet cell types. Alleviation of metabolic stress, ER stress, and maladaptive prostaglandin signaling could improve β-cell function and survival. [Curr Diab Rep] Abstract

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

Lexicon Pharmaceuticals Announces Publication of Positive Data for Zynquista™ (Sotagliflozin) on Cardiorenal Clinical Biomarkers in Adults with Type 1 Diabetes

Lexicon Pharmaceuticals, Inc. announced positive 52-week cardiorenal results from a pooled analysis from the inTandem1 and inTandem2 studies of Zynquista™ in adults with type 1 diabetes. Zynquista demonstrated changes in clinical biomarkers such as estimated glomerular filtration rate, hematocrit, serum albumin, uric acid, systolic blood pressure and urinary albumin-to-creatinine ratio that suggest Zynquista may reduce cardiovascular risk and progression of chronic kidney disease. [Lexicon Pharmaceuticals, Inc.] Press Release

Hyundai Hope on Wheels Presents the University of Illinois at Chicago with $100,000 Hyundai Impact Award Grant to Support Pediatric Cancer Research

Hyundai Hope On Wheels^® announced a $100,000 Hyundai Impact Award Grant to the University of Illinois at Chicago to continue its long-standing fight against pediatric cancer. The institution is one of 77 recipients receiving a combined $16 million in new grants this year to develop innovative approaches to finding a cure for the disease. [Hyundai Hope On Wheels (PR Newswire LLC.)] Press Release

UC Faculty Members Quit Cell Press Editorial Boards over Impasse with Publisher

Some of the University of California’s (UC’s) most prominent scientists have announced they will resign from editorial boards of Cell Press to protest the continuing impasse between its owner, publishing giant Elsevier, and UC over subscription costs and open access to articles. [ScienceInsider] Editorial

Academia to FBI on Monitoring Chinese Scientists: “Tread Carefully”

Nearly two dozen higher education groups warn the government to be cautious when advising US research universities to keep an eye on students and faculty with ties to certain Chinese institutions. [The Scientist] Editorial

NEW Diabetes: Glucose Control and Beyond
January 27-31, 2020
Santa Fe, New Mexico, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Researcher – Auto-Immunity (Benaroya Research Institute)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

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

Postdoctoral Researcher – Type 1 Diabetes Pathogenesis (Karolinska Institutet)

Research Scientist – Endocrine Pancreas Development (Helmholtz Zentrum München)

Postdoctoral Position – Immunology (Roswell Park Cancer Institute)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Fellow – Cancer Drug Response Research (University of Texas at Austin)

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)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Pancreatic Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.