Pancreatic Cell News Volume 8.07 | Feb 21 2017

TOP STORY

Whole-Genome Landscape of Pancreatic Neuroendocrine Tumors

Researchers performed whole-genome sequencing of 102 primary pancreatic neuroendocrine tumors and defined the genomic events that characterize their pathogenesis. They described the mutational signatures they harbor, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Lipid Transport by TMEM24 at ER–Plasma Membrane Contacts Regulates Pulsatile Insulin Secretion

To better understand the molecular basis underlying insulin secretion, scientists characterized TMEM24, a protein enriched in neuroendocrine cells previously suggested to be required for a normal secretory response. They found that TMEM24 is an endoplasmic reticulum (ER) protein that concentrates at ER-plasma membrane contact sites, where it tethers the two bilayers. [Science] Abstract | Press Release | Graphical Abstract

Converting Adult Pancreatic Islet α Cells into β Cells by Targeting both Dnmt1 and Arx

Investigators showed that the α cell regulators Aristaless-related homeobox (Arx) and DNA methyltransferase 1 (Dnmt1) maintain α cell identity in mice. Within three months of Dnmt1 and Arx loss, lineage tracing and single-cell RNA sequencing revealed extensive α cell conversion into progeny resembling native β cells. Physiological studies demonstrated that converted α cells acquire hallmark β cell electrophysiology and showed glucose-stimulated insulin secretion. [Cell Metab] Abstract | Press Release | Graphical Abstract

Genetic Regulatory Signatures Underlying Islet Gene Expression and Type 2 Diabetes

The authors examined genomic, epigenomic, and transcriptomic profiles in human pancreatic islets to understand the links between genetic variation, chromatin landscape, and gene expression in the context of type 2 diabetes (T2D). They found that T2D genome-wide association studies loci were strikingly and specifically enriched in islet regulatory factor X footprints. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release

Identification and Functional Implications of Sodium/Myo-Inositol Cotransporter 1 in Pancreatic Beta-Cells and Type 2 Diabetes Mellitus

Researchers report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (SMIT1) in rat islets and specifically, β-cells. Genetic or pharmacological inhibition of SMIT impaired glucose-stimulated insulin secretion by INS-1E cells, probably via down-regulation of phosphoinositide signaling. [Diabetes] Abstract

Suppression of Islet Homeostasis Protein Thwarts Diabetes Mellitus Progression

The authors reported that in the αTC1.9 mouse α-cell line, islet homeostasis protein (IHoP) was released in response to high-glucose challenge and was found to regulate secretion of glucagon. They also showed that in non-obese diabetic (NOD) mice with diabetes, major histocompatibility complex class II was upregulated in islets. In addition hyperglycemia was modulated in NOD mice via suppression of IHoP utilizing small interfering RNA constructs/approaches. [Lab Invest] Abstract

Delayed Apoptosis Allows Islet β-Cells to Implement an Autophagic Mechanism to Promote Cell Survival

Scientists report dramatic differences in the temporal regulation and engagement of the apoptotic program in primary rodent islets relative to the INS-1 derived 832/13 cell line. As expected, 832/13 cells rapidly induced cell stress markers in response to ER stress or DNA damage and were fully committed to apoptosis, resulting in >80% cell death within 24 hours. [PLoS One] Full Article

PANCREATIC CANCER

An Integrative Approach Unveils FOSL1 as an Oncogene Vulnerability in KRAS-Driven Lung and Pancreatic Cancer

The authors report the identification of a common transcriptional signature across mutant KRAS cancers of distinct tissue origin that includes the transcription factor FOSL1. High FOSL1 expression identified mutant KRAS lung and pancreatic cancer patients with the worst survival outcome. [Nat Commun] Full Article

PAK4 Interacts with p85 Alpha: Implications for Pancreatic Cancer Cell Migration

Scientists found that elevated p21-activated kinase 4 (PAK4) expression is coincident with increased expression levels of c-Met and the p85α subunit of PI3K. They demonstrated that pancreatic cancer cells have a specific motility response to HGF both in 2D and 3D physiomimetic organotypic assays; which could be suppressed by inhibition of PI3K. [Sci Rep] Full Article | Press Release

MicroRNA-155 Controls Exosome Synthesis and Promotes Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma

The authors investigated the mechanisms of gemcitabine (GEM) resistance using a GEM-resistant pancreatic ductal adenocarcinoma (PDAC) cell line that was established by long-term exposure of PDAC cells to GEM. They report that one microRNA, namely miR-155, was detected in a comprehensive transcriptome survey of GEM-resistant PDAC cells and that it controls exosome secretion, thereby inducing GEM resistance in PDAC. [Sci Rep] Full Article

Duffy Antigen Receptor for Chemokines (DARC) Expressing in Cancer Cells Inhibits Tumor Progression by Suppressing CXCR2 Signaling in Human Pancreatic Ductal Adenocarcinoma

Researchers evaluated functions of chemokine receptors using surgical specimens collected from pancreatic ductal adenocarcinoma (PDAC) patients, and PDAC cell lines. CXCR2 expression had no impact on predicting prognosis, but low DARC expression in cancer cells was an independent risk factor for poor prognosis. [Cytokine] Abstract

FoxO Integration of Insulin Signaling with Glucose and Lipid Metabolism

The authors review the role of FoxO6, in contrast with other FoxO isoforms, in health and disease. They review the distinctive mechanism by which FoxO6 integrates insulin signaling to hepatic glucose and lipid metabolism. They highlight the importance of FoxO6 dysregulation in the dual pathogenesis of fasting hyperglycemia and hyperlipidemia in diabetes. [J Endocrinol] Full Article

Type 1 Diabetes Candidate Genes Linked to Pancreatic Islet Cell Inflammation and Beta-Cell Apoptosis

Investigators discuss the current status of type 1 diabetes susceptibility loci and candidate genes with focus on pancreatic islet cell inflammation and β-cell apoptosis. [Genes (Basel)] Full Article

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

Boston Biomedical Initiates CanStem111P: A Global Phase III Study Investigating Cancer Stemness Inhibitor Napabucasin in Patients with Metastatic Pancreatic Cancer

Boston Biomedical has initiated dosing of the first patient in a new global Phase III study, CanStem111P. The study will investigate napabucasin – an orally administered, first-in-class, investigational agent designed to inhibit cancer stemness pathways by targeting STAT3 – in combination with standard of care in patients with metastatic pancreatic cancer. [Boston Biomedical] Press Release

Interpace Diagnostics Enters into Collaborative Agreement with Viatar CTC Solutions to Detect and Characterize Early Cancer in Liquid Biopsies

Interpace Diagnostics Group, Inc. announced the initiation of a collaborative research program with Viatar CTC Solutions Inc. The collaboration utilizes Viatar’s novel circulating tumor cell collection technology in combination with the company’s commercialized PancraGEN™ assay that is used to help assess indeterminate pancreatic cancer biopsies in patients with pancreatic cysts. Studies are being designed to identify patients most likely to develop pancreatic cancer in the near future as well as to detect pancreatic cancer at its earliest stage of development. [Interpace Diagnostics Group, Inc.] Press Release

The Scripps Research Institute Announces New Board Members and Chairman of the Board

The Scripps Research Institute announced the appointment of nine new members to its Board of Directors, including John D. Diekman, who will serve as chairman of the board. Diekman replaces Richard A. Gephardt, who is retiring from the board after seven years of service. [The Scripps Research Institute] Press Release

Delay in Hiring Science Advisers Intensifies Brexit Worries

Policy experts want scientists to be at the table when government decides on environmental protection and membership of international collaborations. [Nature News] Editorial

NEW American Society of Gene & Cell Therapy (ASGCT)
May 10-13, 2017
Washington, DC, United States

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

NEW Lecturer/Senior Lecturer – Pancreatic Cancer (Queen Mary University of London)

NEW Postdoctoral Fellows – Cancer Epigenetics (Baylor Scott & White Research Institute)

NEW Postdoctoral Fellow/ Research Scientist – Diabetes Research (Novo Nordisk)

Senior Scientist – Pancreatic Cell Research (STEMCELL Technologies Inc.)

Postdoctoral Position – Pancreatic Cancer (Cold Spring Harbor Laboratory)

Postdoctoral Fellow – Islet Function/Regeneration (Toronto General Research Institute)

Postdoctoral Fellow – Pancreatic Beta Cell Biology and Regeneration (Icahn School of Medicine at Mount Sinai)

Postdoctoral Associate – Pancreatic Cancer (University of Miami)

Postdoctoral Research Fellow – Pancreatic Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Oncogenic Signaling Pathways of Colorectal/Pancreatic Cancer (German Cancer Research Center)

Postdoctoral Position – Pancreatic Cancer (University of Liege)

Principle Scientist – Translational Development (Celgene Corporation)

Assistant Professor – Molecular Therapeutics (Dartmouth College/Geisel School of Medicine)

Vice President – Pancreatic Cancer Disease Lead (Celgene Corporation)

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.