Intestinal Cell News Volume 4.22 | Jun 15 2018

TOP STORY

Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis

Using a Stat3 loss-of-function approach in two wnt/β-catenin-dependent autochthonous models of sporadic intestinal tumorigenesis, scientists unravelled a complex intracellular process in intestinal epithelial cells that controls the induction of a CD8⁺ T cell based adaptive immune response. [Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Synergistic and Low Adverse Effect Cancer Immunotherapy by Immunogenic Chemotherapy and Locally Expressed PD-L1 Trap

Researchers demonstrated that oxaliplatin (OxP) boosts anti-PD-L1 mAb therapy against murine colorectal cancer. By design of a PD-L1 trap and loading its coding plasmid DNA into a lipid-protamine-DNA nanoparticle, PD-L1 trap was produced transiently and locally in the tumor microenvironment, and synergized with OxP for tumor inhibition. [Nat Commun] Full Article

Hypoxic Tumor Microenvironment Activates GLI2 via HIF-1α and TGF-β2 to Promote Chemoresistance in Colorectal Cancer

Investigators report that hypoxia-inducible factor (HIF-1α) and cancer-associated fibroblasts-secreted TGF-β2 converge to activate the expression of hedgehog transcription factor GLI2 in cancer stem cells, resulting in increased stemness/dedifferentiation and intrinsic resistance to chemotherapy. [Proc Natl Acad Sci USA] Abstract

Cell-of-Origin DNA Methylation Signatures Are Maintained during Colorectal Carcinogenesis

The authors analyzed DNA methylation patterns in colorectal adenomas and identified three biologically defined subclasses that describe different intestinal crypt differentiation stages. [Cell Rep] Full Article | Graphical Abstract

LACTB, a Novel Epigenetic Silenced Tumor Suppressor, Inhibits Colorectal Cancer Progression by Attenuating MDM2-Mediated p53 Ubiquitination and Degradation

Ectopic expression of LACTB suppressed colorectal cancer (CRC) cells proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro and inhibited CRC growth and metastasis in vivo, while knockout of LACTB by CRISPR/Cas9 gene editing technique resulted in an opposite phenotype. [Oncogene] Abstract

β-Catenin/TCF Activity Regulates IGF-1R Tyrosine Kinase Inhibitor Sensitivity in Colon Cancer

Reinforcing β-catenin/T cell factor (TCF) responsive promoter activity by introducing CTNNB1 gain-of-function mutations into IGF-1R/IR tyrosine kinase inhibitor (TKI)-resistant cells increased the expression and activity of IGF-1R/IR signaling components and also sensitized the cells to IGF-1R/IR TKIs in vitro and in vivo. [Oncogene] Abstract

BVES Is Required for Maintenance of Colonic Epithelial Integrity in Experimental Colitis by Modifying Intestinal Permeability

Two different human cell lines co-cultured with enteropathogenic E. coli showed increased attaching/effacing lesions in the absence of blood vessel epicardial substance (BVES). BVES mRNA levels were reduced in human ulcerative colitis biopsy specimens. [Mucosal Immunol] Abstract

DNA Mismatch Repair Protein Deficient Non-Neoplastic Colonic Crypts: A Novel Indicator of Lynch Syndrome

Investigators determined if mismatch repair protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. [Mod Pathol] Abstract

Magnolin Promotes Autophagy and Cell Cycle Arrest via Blocking LIF/Stat3/Mcl-1 in Human Colorectal Cancers

The authors report the role of magnolin in suppressing human colorectal cancer cells via activating autophagy and cell cycle arrest in vitro and in vivo. [Cell Death Dis] Full Article

Dro1/Ccdc80 Inactivation Promotes AOM/DSS Induced Colorectal Carcinogenesis and Aggravates Colitis by DSS in Mice

Combined treatment with azoxymethane (AOM) and dextran sodium sulfate (DSS) lead to increased colonic tumor number and promoted formation of adenocarcinoma in the colon. Moreover, Dro1 inactivation aggravated histological signs of acute and chronic DSS induced colitis, strongly enlarged the size of ulcerative lesions in the intestinal lining, and exacerbated clinical signs and morbidity by DSS. [Carcinogenesis] Abstract

Alterations of mTOR Signaling Impact Metabolic Stress Resistance in Colorectal Carcinomas with BRAF and KRAS Mutations

Scientists investigated how BRAF^V600E and KRAS^G12V affect cell metabolism, stress resistance and signaling in colorectal carcinoma cells driven by these mutations. [Sci Rep] Full Article

The Current State of the Art for Biological Therapies and New Small Molecules in Inflammatory Bowel Disease

The authors summarize the current state of the art for biological therapies in inflammatory bowel disease (IBD), both in terms of agents available and their optimal use, as well as preview future advances in biologics and highly targeted small molecules in the IBD field. [Mucosal Immunol] Abstract

Application of Porcine Gastrointestinal Organoid Units as a Potential In Vitro Tool for Drug Discovery and Development

Scientists focus on the culture and establishment of porcine organoid units and their potential use and application as in vitro models to further the science of drug discovery, by overcoming current limitations of established two‐ and three‐dimensional models. [J Appl Toxicol] Abstract

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

The Scripps Research Institute and ShangPharma Innovation Announce Translational Research Collaboration

The Scripps Research Institute and ShangPharma Innovation, Inc. announced a strategic collaboration to accelerate the development of innovative drug candidates through scientific collaboration, a services relationship with Shanghai ChemPartner Co. Ltd., and sponsored research at TSRI and its drug discovery affiliate, California Institute for Biomedical Research. [The Scripps Research Institute] Press Release

National Cancer Institute Selects ASU to Lead Revolutionary Research in Cancer

Arizona State University (ASU) has been awarded more than $8.5 million over five years from the National Cancer Institute to establish the Arizona Cancer and Evolution Center. The grant will establish ASU as the hub of an international network of research scientists who are dedicated to understanding cancer in an entirely new way. [Arizona State University] Press Release

Learn the basics of culturing mouse intestinal organoids with an instructional video series. Watch the Video Now

New Zealand Appoints First Female Chief Scientific Adviser

The New Zealand government has appointed biochemist Juliet Gerrard as its next chief scientific adviser — the first woman to hold the position. [Nature News] Editorial

Leading Salk Scientist Resigns after Allegations of Harassment

The prominent cancer biologist Inder Verma unconditionally resigned from the Salk Institute for Biological Studies in San Diego, California, June 6, and the research institute’s board of trustees voted unanimously to accept his resignation. [ScienceInsider] Editorial

China Introduces Sweeping Reforms to Crack Down on Academic Misconduct

China is getting tough on scientific misconduct. The country’s most powerful bodies, the Chinese Communist Party and the State Council, introduced a raft of reforms on 30 May aimed at improving integrity across the research spectrum, from funding and job applications to peer-review and publications. [Nature News] Editorial

NEW LabRoots: 6^th Annual Cancer Research & Oncology Virtual Event
October 10-11, 2018
Online

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

NEW PhD position – Inflammatory Bowel Disease (Universitätsmedizin Berlin)

Postdoctoral Fellow Position – Intestinal Research (Vanderbilt University Medical Center)

Postdoctoral Position – Cancer Biology and Metastasis (MD Anderson Cancer Center)

Associate/Full Researcher – Cancer Biology (University of Hawaii Cancer Center)

Postdoctoral Position – Human Mucosal Immunology/Inflammatory Bowel Disease (Weill Cornell Medicine)

Postdoctoral Positions – Colon Stem Cells and Carcinogenesis (Johns Hopkins University School of Medicine)

Postdoctoral Fellowship – Inflammatory Bowel Disease (European Molecular Biology Laboratory)

Postdoctoral Position – Technology-Driven Research in Biomedicine (CeMM Research Center for Molecular Medicine)

Academic Position – Cancer Research (Cedars-Sinai Medical Center)

PhD Student – Endocrine Cells in the Gut (Helmholtz Zentrum München)

Postdoctoral Position – Digestive Health (University of California, Irvine)

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

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