Intestinal Cell News Volume 5.35 | Sep 20 2019

TOP STORY

Suppressive and Gut Reparative Functions of Human Type 1 T-regulatory Cells

Human colon organoid cultures were established, cultured with supernatants from type 1 Treg (Tr1) or FOXP3-positive cells, and analyzed by immunofluorescence and flow cytometry. T84 cells were incubated with supernatants from Tr1 or FOXP3-positive cells and trans-epithelial electrical resistance was measured to determine epithelial cell barrier function. [Gastroenterology] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

An Aggregon in Conductin/Axin2 Regulates Wnt/β-Catenin Signaling and Holds Potential for Cancer Therapy

By domain swapping between axin and conductin researchers identified an aggregation site in the conductin RGS domain which prevented conductin polymerization. Induction of conductin polymerization by point mutations of this aggregon resulted in enhanced inhibition of Wnt/β-catenin signaling. [Nat Commun] Full Article

VAMP8-Mediated MUC2 Mucin Exocytosis from Colonic Goblet Cells Maintains Innate Intestinal Homeostasis

Investigators describe how the vesicle SNARE protein VAMP8 coordinated mucin exocytosis from goblet cells. Vamp8^−/− exhibited a mild pro-inflammatory state basally due to an altered mucus layer and increased encounters with microbial antigens. Microbial diversity shifted to a detrimental microbiota with an increase abundance of pathogenic and mucolytic bacteria. [Nat Commun] Full Article

USP22 Exerts Tumor-Suppressive Functions in Colorectal Cancer by Decreasing mTOR Activity

Scientists sought to investigate the role of Usp22 during tumorigenesis in vivo using a mouse model for intestinal carcinogenesis with a tissue-specific Usp22 ablation. In addition, they assessed the effects of USP22 depletion in human colorectal cancer cells on tumorigenic potential and identified underlying molecular mechanisms. [Cell Death Differ] Abstract

LINC00265 Promotes Colorectal Tumorigenesis via ZMIZ2 and USP7-Mediated Stabilization of β-Catenin

Mechanistically, LINC00265 augmented ZMIZ2 expression by acting as an endogenous sponge against several miRNAs, which directly targeted ZMIZ2 expression. Moreover, ZMIZ2 recruited the enzyme USP7, which deubiquitylates and stabilized β-catenin, thereby facilitating colorectal tumorigenesis. [Cell Death Differ] Abstract

Control of Intestinal Cell Fate by Dynamic Mitotic Spindle Repositioning Influences Epithelial Homeostasis and Longevity

Using a combination of long-term live imaging, lineage tracing, and genetic perturbations, the authors demonstrated that the asymmetric to symmetric lineage switch was executed through the control of mitotic spindle orientation by Jun-N-terminal kinase (JNK) signaling. JNK interacted with the WD40-repeat protein Wdr62 at the spindle and transcriptionally repressed the kinesin Kif1a to promote planar spindle orientation. [Cell Rep] Full Article | Graphical Abstract

Non-Hematopoietic STAT6 Induces Epithelial Tight Junction Dysfunction and Promotes Intestinal Inflammation and Tumorigenesis

Mechanistically, long-myosin light-chain kinase (MLCK1) was identified as a target of STAT6, leading to epithelial tight junction dysfunction and microbiota-driven colitis. Furthermore, neutralization of IL-13, which was primarily derived from type 2 innate lymphoid cells in a microbiota-dependent way, inhibited epithelial STAT6 activation and improved gut permeability and DSS-induced colitis. [Mucosal Immunol] Full Article

AMPKα1 Confers Survival Advantage of Colorectal Cancer Cells under Metabolic Stress by Promoting Redox Balance through the Regulation of Glutathione Reductase Phosphorylation

Researchers revealed a previously unrecognized function of AMPKα1, which maintained high level of reduced glutathione to keep reduction-oxidation reaction (redox) homeostasis under stress conditions, thus promoting colorectal cancer cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPKα1 regulated the glutathione reductase phosphorylation possibly through residue Thr507 which enhances its activity. [Oncogene] Full Article

BTK Inhibitors Synergize with 5-FU to Treat Drug-Resistant TP53-Null Colon Cancers

Using drug-resistant TP53-null colon cancer cells as a model investigators demonstrated that p65BTK silencing or chemical inhibition overcame the 5-fluorouracil (F-FU) resistance of colorectal cancer cell lines and patient-derived organoids and significantly reduced the growth of xenografted tumours. Mechanistically, they showed that blocking p65BTK in drug-resistant cells abolished a 5-FU-elicited TGFB1 protective response and triggered E2F-dependent apoptosis. [J Pathol] Abstract

RNA-Binding Protein CELF6 Is Cell Cycle Regulated and Controls Cancer Cell Proliferation by Stabilizing p21

The cell cycle-dependent expression of CELF6 was mediated through the ubiquitin-proteasome pathway, SCF-β-TrCP recognized a nonphospho motif in CELF6 and regulated its proteasomal degradation. Overexpression or depletion of CELF6 modulated p21 gene expression. [Cell Death Dis] Full Article

The Mechanism of the Premetastatic Niche Facilitating Colorectal Cancer Liver Metastasis Generated from Myeloid-Derived Suppressor Cells Induced by the S1PR1-STAT3 Signaling Pathway

Immunohistochemistry was used to detect sphingosine-1-phosphate receptor 1 and signal transducer and activator of transcription-3 in human colorectal tumors. IL-6 and interferon-γ were detected by enzyme-linked immunosorbent assay. Tumor growth, invasion, and migration were evaluated by MTT, transwell, and wound healing assays, respectively. [Cell Death Dis] Full Article

Expression Analysis and Implication of Rab1A in Gastrointestinal Relevant Tumor

Rab1A knockdown significantly inhibited the in vitro proliferation and migration abilities of gastric cancer (GC) cells, as well as the growth of GC xenografts in vivo. Furthermore, a positive correlation was observed between Rab1A expression levels and that of different upstream/downstream mTOR targets. [Sci Rep] Full Article

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

Microsatellite Instability and Immune Checkpoint Inhibitors: Toward Precision Medicine against Gastrointestinal and Hepatobiliary Cancers

The authors describe the molecular basis of the MMR pathway, diagnostics of microsatellite instability (MSI) status, and the clinical importance of MSI status and the tumor mutation burden in developing therapeutic strategies against gastrointestinal and hepatobiliary malignancies. [J Gastroenterol] Full Article

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

Ironwood Pharmaceuticals and AstraZeneca Amend LINZESS^® (Linaclotide) Collaboration in China

Ironwood Pharmaceuticals, Inc. announced that it has amended its collaboration agreement with AstraZeneca for the development and commercialization of LINZESS in China. LINZESS was approved by the National Medical Products Administration for adults with IBS-C in China in January 2019. [Ironwood Pharmaceuticals, Inc.] Press Release

Tonix Pharmaceuticals Announces Licensing Agreement with Columbia University for the Development of Recombinant Trefoil Family Factor 2 (rTFF2), or TNX-1700, for the Treatment of Gastric and Pancreatic Cancers

Tonix Pharmaceuticals Holding Corp. announced that it has obtained an exclusive license from Columbia University for the development of TNX-1700 for the treatment of gastric and pancreatic cancers. TNX-1700 is a biologic currently in pre-clinical development. [Tonix Pharmaceuticals Holding Corp.] Press Release

Innovation Pharmaceuticals Announces Successful Formulation of Oral Brilacidin Tablets; Upcoming Clinical Trial to Target Delivery to the Colon

Innovation Pharmaceuticals announced that BDD Pharma, the company’s formulation partner in the area of IBD, has performed appropriate non-clinical studies that show the oral dosage form meets in vitro specifications for selective delivery of oral Brilacidin to the colon. [Innovation Pharmaceuticals] Press Release

Kashmir’s Communication Blackout Is a ‘Devastating Blow’ for Academics, Researchers Say

Six professors from India’s top science institutions have appealed to the government to lift the blockade of academic and research institutions in Indian-controlled Kashmir. The blockade has been a “devastating blow,” the six write in an open letter published September 18^th. [ScienceMagazine] Editorial

New Journal Seeks Typically Overlooked Studies

On September 18, Cambridge University Press launched an open-access journal that will address issues in research by taking a different approach to publishing. The journal, Experimental Results, will include findings that have inconclusive or negative results and articles that reproduce or dispute existing research. [The Scientist] Editorial

US Awards $3 Million to Fill Gaps in Medical Marijuana Research

The US government will spend $3 million to find out if marijuana can relieve pain, but none of the money will be used to study the part of the plant that gets people high. Nine research grants announced are for work on CBD, the trendy ingredient showing up in cosmetics and foods, and hundreds of less familiar chemicals. THC research was excluded. [STAT News] Editorial

NEW AACR International Conference on Molecular Targets and Cancer Therapeutics
October 26-30, 2019
Boston, Massachusetts, United States

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

NEW Research Scientist – Inflammatory Diseases (Texas A&M Agrilife)

Research Technologist – Intestinal Stem Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Systems Biology of Cancer (Max Planck Institute for Molecular Genetics)

Postdoctoral Fellow – Intestinal Graft-versus-Host-Disease (Medical College of Wisconsin)

Senior Researcher – Inflammatory Diseases (Genentech, Inc.)

Postdoctoral Researcher – Microbiome in IBD (GIGA-Medical Genomics Unit)

Postdoctoral Fellow – Quantifying Intra-tumour Heteregeneity with Multi-Omics Data (The Institute of Cancer Research)

Postdoctoral Fellow – Designer Probiotics (Massacheusetts General Hospital)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

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

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.