Intestinal Cell News Volume 5.15 | May 3 2019

TOP STORY

Ongoing Chromosomal Instability and Karyotype Evolution in Human Colorectal Cancer Organoids

Using three-dimensional live-cell imaging of patient-derived tumor organoids (tumor PDOs), researchers showed that chromosomal instability was widespread in colorectal carcinomas regardless of background genetic alterations, including microsatellite instability. Cell-fate tracking showed that, although mitotic errors are frequently followed by cell death, some tumor PDOs were largely insensitive to mitotic errors. [Nat Genet] Abstract

(Ranked by impact factor of the journal)

Nutrient Sensing by the Intestinal Epithelium Orchestrates Mucosal Antimicrobial Defense via Translational Control of Hes1

Scientists showed that the antimicrobial peptide α-defensin was functionally sustained during nutrient deprivation because of regulation of the defensin-processing enzyme MMP7 by microbiota- and host-derived factors. Unlike other antimicrobial peptides, the MMP7-α-defensin axis remained active during nutrient fluctuations, providing essential protection against enteric pathogens. [Cell Host Microbe] Abstract | Graphical Abstract

Acetylation of PHF5A Modulates Stress Responses and Colorectal Carcinogenesis through Alternative Splicing-Mediated Upregulation of KDM3A

Investigators uncovered a list of hyperacetylated proteins in the context of acutely reduced Acetyl-CoA levels under nutrient starvation. PHF5A, a component of U2 snRNPs, could be acetylated at lysine 29 in response to multiple cellular stresses, which was dependent on p300. PHF5A acetylation strengthened the interaction among U2 snRNPs and affects global pre-mRNA splicing pattern and extensive gene expression. [Mol Cell] Abstract | Graphical Abstract

Physical and Functional Interaction between A20 and ATG16L1-WD40 Domain in the Control of Intestinal Homeostasis

The authors showed that the anti-inflammatory protein A20 and the critical autophagic mediator Atg16l1 physically interacted and synergized to regulate the stability of the intestinal epithelial barrier. A proteomic screen using the WD40 domain of ATG16L1 identified A20 as a WDD-interacting protein. [Nat Commun] Full Article

The H2A.Z Histone Variant Integrates Wnt Signaling in Intestinal Epithelial Homeostasis

Researchers studied the involvement of H2A.Z in intestinal epithelial homeostasis, which was dependent on the finely-tuned equilibrium between stem cell renewal and differentiation, under the control of such a pathway. They used cell models and inducible knock-out mice to study the impact of H2A.Z depletion on intestinal homeostasis. [Nat Commun] Full Article

An Inhibitor of the Pleckstrin Homology Domain of CNK1 Selectively Blocks the Growth of Mutant KRAS Cells and Tumors

The authors showed that selective inhibition of Cnk1 blocked growth and Raf/Mek/Erk, Rho and RalA/B signaling in mut-KRAS lung and colon cancer cells with little effect on wild type-KRAS cells. Cnk1 inhibition decreased anchorage-independent mut-KRas cell growth more so than growth on plastic, without the partial ‘addiction’ to mut-KRAS seen on plastic. [Cancer Res] Abstract

Integrated In Vitro and In Silico Modeling Delineates the Molecular Effects of a Synbiotic Regimen on Colorectal-Cancer-Derived Cells

Investigators expanded their HuMiX gut-on-a-chip model to co-culture colorectal cancer-derived epithelial cells with a model probiotic under a simulated prebiotic regimen, and they integrated the multi-omic results with in silico metabolic modeling. In contrast to individual prebiotic or probiotic treatments, the synbiotic regimen caused downregulation of genes involved in procarcinogenic pathways and drug resistance, and reduced levels of the oncometabolite lactate. [Cell Rep] Full Article | Graphical Abstract

Non-Canonical HIF-1 Stabilization Contributes to Intestinal Tumorigenesis

Intestinal epithelial cell-specific Hif1a loss reduced activation of Wnt/β-catenin, tumor-specific metabolism and inflammation, significantly inhibiting tumor growth. Deletion of Hif1a in myeloid cells reduced the expression of fibroblast-activating factors in tumor-associated macrophages resulting in decreased abundance of tumor-associated fibroblasts and robustly reduced tumor formation. [Oncogene] Abstract

PTPRB Promotes Metastasis of Colorectal Carcinoma via Inducing Epithelial-Mesenchymal Transition

Investigators showed that protein tyrosine phosphatase, receptor type B (PTPRB) promoted metastasis of colorectal cancer (CRC) cells via inducing epithelial-mesenchymal transition. They found that PTPRB was expressed at significantly higher levels in CRC tissues compared to adjacent nontumor tissues and in CRC cell lines with high invasion. PTPRB knockdown decreased the number of invasive CRC cells in an in vitro wound healing model, and also reduced tumor metastasis in vivo. [Cell Death Dis] Full Article

Immunoprofiling of Colitis-Associated and Sporadic Colorectal Cancer and Its Clinical Significance

Researchers compared the expression levels of various surface markers in immune cells between colitis-associated cancer (CAC) and sporadic colorectal cancer (CRC) and evaluated the clinical usefulness of immunoprofiling in CRC. Tumor specimens from 24 CAC patients and 48 sporadic CRC patients, matched by age, sex, and tumor location to CAC, were included in the analysis. [Sci Rep] Full Article

JIB-04, a Small Molecule Histone Demethylase Inhibitor, Selectively Targets Colorectal Cancer Stem Cells by Inhibiting the Wnt/β-Catenin Signaling Pathway

Scientists showed that JIB-04, a pan-selective inhibitor of histone demethylase(s), was identified as a small molecule that selectively target colorectal cancer stem cells (CSCs). Their data showed that JIB-04 was capable of reducing self-renewal and stemness of colorectal CSCs in three different colorectal cancer cell lines. JIB-04 significantly attenuated CSC tumorsphere formation, growth/relapse, invasion, and migration in vitro. [Sci Rep] Full Article

Subscribe to one of our other 19 science newsletters such as Pulmonary Cell News & ESC & iPSC News.

An Update on the Morphology and Molecular Pathology of Serrated Colorectal Polyps and Associated Carcinomas

The authors summarize the current understanding of serrated polyps and associated carcinomas with a focus on diagnostic criteria, morphologic heterogeneity, molecular findings, and natural history. Controversial issues in the diagnosis and classification of these polyps are also discussed. [Mod Pathol] Abstract

The Role of Autophagy in Maintaining Intestinal Mucosal Barrier

Investigators aim to elucidate the myriad roles of autophagy in regulating the functions of different intestinal epithelial cells, and present the progress of autophagy-targeting therapy in intestinal diseases. Understanding the involved mechanisms can provide new preventive and therapeutic strategies for gastrointestinal dysfunction and diseases. [J Cell Physiol] Abstract

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

Abivax Receives First Phase IIb Ulcerative Colitis Clinical Trial Authorization, Provides Update on Progress of ABX464 Clinical Development Plan in Inflammatory Diseases

Abivax announced that Canada is the first country to have fully authorized its Phase IIb clinical trial design for ABX464 to treat ulcerative colitis. The first patient is expected to be enrolled in the study in Q2 2019. In addition to Canada, the clinical trial will largely be conducted in Europe. [ABIVAX] Press Release

SunGen Pharma Receives Its Fourth and Fifth ANDA Approvals from US FDA

SunGen Pharma announced it has received its fourth and fifth ANDA approvals from the FDA. The fifth approved ANDA is a generic version of Bentyl^®, Dicyclomine Hydrochloride Injection USP, 20 mg/2 mL (10 mg/mL). It is a sterile injectable solution in 2mL-vial in cartons of 5. Dicylomine is used to treat a certain type of intestinal problem called irritable bowel syndrome. [SunGen Pharma (GlobeNewswire, Inc.)] Press Release

Fondren Foundation Commits $15 Million to Houston Methodist to Pioneer Treatments

The Fondren Foundation has made a $15 million commitment to Houston Methodist to support the Food and Health Alliance, the Immunology Center and to create the Fondren Inflammation Collaborative, a new multidisciplinary program that will provide hope for people with complex allergy, immunologic, autoimmune and GI conditions. [The American Association for the Advancement of Science] Press Release

Change Makers across the Oncology Community Recognized at 2019 Cancer Community (C2) Awards

The oncology community gathered together last night to celebrate the winners of the first Cancer Community Awards. These awards recognize individuals and organizations who have created positive change in cancer care. The awards – a partnership between AstraZeneca and Scientific American Custom Media – includes nominations submitted by organizations from across the cancer ecosystem and participation from an esteemed panel of third-party judges. [Cancer Community (C2) Awards (Business Wire, Inc.)] Press Release

Dr. Tamara Zietek discusses the use of intestinal organoids as a model system for nutrient transport. Listen Now

Global Health Institute Sued for Age and Sex Discrimination

Seven current and former female employees have sued officials at a global health institute that is part of the Mount Sinai Health System’s Ichan School of Medicine in New York City, claiming age and sex discrimination. [ScienceInsider] Editorial

Shake-Up at NIH: Term Limits for Important Positions Would Open New Opportunities for Women, Minorities

The NIH is aiming to shake up its intramural program, the largest collection of biomedical researchers in the world, by imposing term limits on midlevel leadership positions. Starting next year, the 272 lab and branch chiefs who oversee NIH’s intramural research will be limited to 12-year terms. [ScienceInsider] Editorial

Senator’s Queries Prompt NIH and NSF to Clarify How They Monitor Foreign Research Ties

Responding to the rising concern within Congress that foreign governments are taking advantage of the open US research enterprise, the National Institutes of Health (NIH) and the National Science Foundation (NSF) have recently tweaked their grantmaking process to better monitor the foreign ties of the researchers they fund. [ScienceInsider] Editorial

NEW 18th^th International Celiac Disease Symposium
September 5-7, 2019
Paris, France

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

NEW Postdoctoral Researcher – Intestinal Immunology (KU Leuven)

NEW Postdoctoral Director – mRNA Treatment for Rare Diseases (Moderna)

Postdoctoral Researcher – Gastrointestinal Cancer & IBD (Case Western Reserve University)

Postdoctoral Position – Functional Genomics of IBS (Wellcome Sanger Institute)

Postdoctoral Position – Oesophago-Gastric Cancer Research (University of Cambridge)

Postdoctoral Position – IBS and Autoimmune Disease (National Research Council of Canada)

Postdoctoral Position – Animal Genomics & IBD (University of Liège)

Graduate Student Position – Breast & Colorectal Cancer Research (Dalhousie University)

Postdoctoral & Research Associate Positions – Biology of Intestinal & Colon Stem Cells & Gastrointestinal Cancer (Johns Hopkins University)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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 Intestinal Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.