Intestinal Cell News Volume 5.46 | Dec 6 2019

TOP STORY

Tissue-Specific Transcription Reprogramming Promotes Liver Metastasis of Colorectal Cancer

Using clinical samples, patient-derived xenograft (PDX) samples, PDX cells, and primary/metastatic cell lines, researchers discovered that liver metastatic colorectal cancer cells lose their colon-specific gene transcription program yet gained a liver-specific gene transcription program. They showed that this transcription reprogramming was driven by a reshaped epigenetic landscape of both typical enhancers and super-enhancers. [Cell Res] Abstract

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Heterogeneity and Dynamics of Active Kras-Induced Dysplastic Lineages from Mouse Corpus Stomach

Investigators established metaplastic and dysplastic organoid lines, derived from Mist1-Kras mouse stomach corpus and studied distinct cellular behaviors and characteristics of metaplastic and dysplastic organoids. They also examined functional roles for Kras activation in dysplasia progression using Selumetinib, a MEK inhibitor, which was a downstream mediator of Kras signaling. [Nat Commun] Full Article

Extensive Subclonal Mutational Diversity in Human Colorectal Cancer and Its Significance

The authors applied duplex sequencing methodology to quantify subclonal mutations in colorectal cancer (CRC) tumor with unprecedented depth and accuracy. They measured mutation frequencies in genes encoding replicative DNA polymerases and in genes frequently mutated in CRC, and found an unexpectedly high effective mutation rate, 7.1×10^-7. [Proc Natl Acad Sci USA] Full Article

Age-Onset Phosphorylation of a Minor Actin Variant Promotes Intestinal Barrier Dysfunction

Scientists showed that an uncharacterized phosphorylation of a low-abundant actin variant, ACT-5, compromised integrity of the C. elegans intestinal barrier and accelerated pathogenesis. Age-related loss of the heat-shock transcription factor, HSF-1, disrupted the JUN kinase and protein phosphatase I equilibrium which increased ACT-5 phosphorylation within its troponin binding site. [Dev Cell] Abstract | Graphical Abstract

Macrophage-Derived CCL5 Facilitates Immune Escape of Colorectal Cancer Cells via the p65/STAT3-CSN5-PD-L1 Pathway

Researchers demonstrated that macrophage infiltration induced by lipopolysaccharide or a high-cholesterol diet significantly promoted colorectal cancer growth. Similarly, LPS and poly remarkably increased the volume of CT26 cell allograft tumors. C-C motif chemokine ligand 5 (CCL5), which was secreted by macrophages, inhibited T-cell-mediated killing of HT29 cells and promoted immune escape by stabilizing PD-L1 in vitro and in vivo. [Cell Death Differ] Abstract

Gastric Cancer-Derived Mesenchymal Stromal Cells Trigger M2 Macrophage Polarization That Promotes Metastasis and EMT in Gastric Cancer

The importance of macrophages in the pro-tumor role of gastric cancer-derived mesenchymal stromal cells (GC-MSCs) was observed in a mouse xenograft model with macrophage depletion. In gastric cancer tissues, high expression levels of Ym-1, Fizz-1, arginase-1, and CCR-2, as well as a low expression level of iNOS, were verified, and co-localization of GC-MSCs and tumor-associated macrophages was observed by dual immunofluorescence histochemistry. [Cell Death Dis] Full Article

Identification of a Small Compound Targeting PKM2-Regulated Signaling Using 2D Gel Electrophoresis-Based Proteome-Wide CETSA

Scientists developed a modified method by combining the cellular thermal shift assay (CETSA) and proteomics analysis based on 2D gel electrophoresis, namely 2DE-CETSA, to identify the thermal stability-shifted proteins by binding with a new compound. They applied the 2DE-CETSA for analysis of a target-unknown compound, NPD10084, which exerted anti-proliferative activity against colorectal cancer cells in vitro and in vivo, and identified pyruvate kinase muscle isoform 2 (PKM2) as a candidate target protein. [Cell Chem Biol] Abstract | Graphical Abstract

Transcriptome Changes in Undifferentiated Caco-2 Cells Exposed to Food-Grade Titanium Dioxide (E171): Contribution of the Nano- and Micro- Sized Particles

The authors investigated the relative contribution of the nanoparticles (NPs) and microparticles (MPs) to effects of E171 at the transcriptome level in undifferentiated Caco-2 cells by genome wide microarray analysis. The results showed that E171, NPs, and MPs induce gene expression changes related to signaling, inflammation, immune system, transport and cancer. [Sci Rep] Full Article

β-Catenin Activation Down-Regulates Cell-Cell Junction-Related Genes and Induces Epithelial-to-Mesenchymal Transition in Colorectal Cancers

Researchers investigated β-catenin localization, transcriptome, and phenotypic differences of HCT116 cells containing a wild-type or mutant β-catenin allele, or parental cells with both wild-type and mutant alleles. They then analyzed β-catenin expression and associated phenotypes in colorectal cancer tissues. [Sci Rep] Full Article

IFN-γ and IL-17A Regulate Intestinal Crypt Production of CXCL10 in the Healthy and Inflamed Colon

IFN-γ induced the TH₁-recruiting, pro-inflammatory chemokine CXCL10/IP10 in primary murine intestinal crypt epithelium. CXCL10 was also induced in colonic spheroids derived from mice with active, experimentally-induced colitis, suggesting that the crypt could actively secrete CXCL10 in select cytokine environments during colitis. [Am J Physiol Gastrointest Liver Physiol] Abstract

Non-Extractable Polyphenols From Cranberries: Potential Anti-Inflammation and Anti-Colon-Cancer Agents

Results showed that of the identified polyphenols, anthocyanins were the major ones in the cranberry extractable polyphenols (EP) fraction, while phenolic acids were most abundant in the non-EP (NEP) fraction. The oxygen radical absorbance capacity of the NEPs was significantly higher than that of the EPs. Both the EPs and NEPs showed anti-inflammatory effects in inhibiting LPS-induced production of nitric oxide in macrophages. [Food Funct] Abstract

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Molecular Anatomy and Pathogenic Actions of Helicobacter pylori CagA That Underpin Gastric Carcinogenesis

Analysis of CagA using in vitro cultured gastric epithelial cells indicated that the nonphysiological scaffolding actions of CagA cell-autonomously promote the malignant transformation of the cells by endowing the cells with multiple phenotypic cancer hallmarks: sustained proliferation, evasion of growth suppressors, invasiveness, resistance to cell death, and genomic instability. [Cell Mol Immunol] Full Article

Vitamin D and the Nutritional Environment in Functions of Intestinal Stem Cells: Implications for Tumorigenesis and Prevention

The data establish a key role of the nutrient environment, and vitamin D signaling, in defining contribution of at least two different stem cell populations to mucosal homeostasis and tumorigenesis. This raises significant questions regarding impact of variable human diets on which and how multiple potential intestinal stem cell populations function in the human and give rise to tumors. [J Steroid Biochem Mol Biol] Abstract

Intestinal Organoids for Cystic Fibrosis Research

Heterogeneity in in vivo modulator response has been reported among individuals carrying homozygous F508del-CFTR, adding to the desire for an optimal prediction of response-to-therapy on an individual level. In the last decade, a lot of progress has been made in the development of primary cell cultures into 3D patient-derived disease models. [J Cyst Fibros] Full Article

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Cold Spring Harbor Lab Wins Grant for Cancer Research

Cold Spring Harbor Laboratory has won a $750,000 grant from TD Bank to support its new cancer research facility. The award is part of the TD Ready Challenge, an initiative to provide financial support to organizations that have developed solutions to improve detection and intervention of diseases. [Sacred Heart University] Press Release

U of T Professor Wins Grant to Study How Online Psychotherapy Can Help Children With Inflammatory Bowel Disease

Dr. Sara Ahola Kohut, a researcher at the Hospital of Sick Kids and an assistant professor at the Univeristy of Toronot (U of T), received a $50,000 grant from Crohn’s and Colitis Canada to research the promise of online acceptance and commitment therapy workshops in supporting children with inflammatory bowel disease and their families. [The Varsity] Press Release

Science Publishers Review Ethics of Research on Chinese Minority Groups

Two science publishers are reviewing the ethics of research papers in which scientists backed by China’s government used DNA or facial-recognition technology to study minority groups in the country, such as the predominantly Muslim Uyghur population. [Nature News] Editorial

What the United Kingdom’s ‘Brexit Election’ Means for Science

The United Kingdom’s three main political parties have each pledged to increase spending on science, ahead of a general election overshadowed by the country’s vote three and a half years ago to leave the European Union. [Nature News] Editorial

NEW 4^th DNA Repair/Replication Structures and Cancer Conference
February 16-20, 2020
Nassau, Bahamas, United States

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NEW Researcher – Synthetic Ecology of Human Gut Microbiota (Flanders Institute for Biotechnology)

Assistant Professor – Intestinal Microbiota and Immunity (Hokkaido University)

Assistant Professor – Intestinal Microbiota Immunology (Hokkaido University)

Research Position – Microscopy of Human Tumors (Vienna University of Technology)

Postdoctoral Researcher – Mucosal Immunology (KU Leuven)

Postdoctoral Fellow – Neonatal Microbiota on Immune Imprinting (Pasteur Institute)

Research Fellow – Intestinal In Vivo/In Vitro Correlations (AbbVie)

Postdoctoral Fellow – Gut Microbiome & IBD (Case Western Reserve University)

Postdcotoral Scientist – iPSC Models of Intestinal Fibrosis (Cedars-Sinai Medical Center)

Senior Scientist – Immunology and Gastroenterology (Johnson & Johnson)

Research Scientist – In Vivo Research on Wnt Signaling in Self-Renewel (Surrozen)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

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