Intestinal Cell News Volume 6.15 | May 1 2020

TOP STORY

Pooled In Vitro and In Vivo CRISPR-Cas9 Screening Identifies Tumor Suppressors in Human Colon Organoids

Scientists identified TGFBR2 as the most prevalent tumor suppressor gene, followed by known and previously uncharacterized mediators of colorectal cancer growth. [Cell Stem Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Discovery and Pharmacological Characterization of AZD3229, a Potent KIT/PDGFRα Inhibitor for Treatment of Gastrointestinal Stromal Tumors

Investigators report the discovery and pharmacological characterization of AZD3229, a potent and selective small-molecule inhibitor of KIT and platelet-derived growth factor α (PDGFRα) designed to inhibit a broad range of primary and imatinib-resistant secondary mutations seen in gastrointestinal stromal tumors. [Sci Transl Med] Abstract

Long Non-Coding RNA RAMS11 Promotes Metastatic Colorectal Cancer Progression

A FDA-approved drug high-throughput viability assay showed that elevated RNAs associated with metastasis (RAMS)11 expression increased resistance to topoisomerase inhibitors. Subsequent experiments demonstrated RAMS11-dependent recruitment of chromobox protein 4 transcriptionally activated topoisomerase II alpha. [Nat Commun] Full Article

Astrovirus Infects Actively Secreting Goblet Cells and Alters the Gut Mucus Barrier

Using an in vivo model, the authors report that murine astrovirus preferentially infected actively secreting small intestinal goblet cells, specialized epithelial cells that maintain the mucus barrier. [Nat Commun] Full Article

Drosophila as a Model for Studying Cystic Fibrosis Pathophysiology of the Gastrointestinal System

Investigators showed that knockdown of Dmelcystic fibrosis (CF) transmembrane conductance regulator (CFTR) in the adult intestine disrupted osmotic homeostasis and displayed CF-like phenotypes that led to intestinal stem cell hyperplasia. [Proc Natl Acad Sci USA] Abstract

The Apoptosome Molecular Timer Synergises with XIAP to Suppress Apoptosis Execution and Contributes to Prognosticating Survival in Colorectal Cancer

Researchers demonstrated that cooperative recruitment of PC9 to the apoptosome, based on existing PC9-apoptosome interaction data, was important for efficient formation of PC9 homodimers, autocatalytic cleavage and dual regulation by XIAP and the molecular timer across biologically relevant PC9 and APAF1 concentrations. [Cell Death Differ] Full Article

Compensation between Wnt-Driven Tumorigenesis and Cellular Responses to Ribosome Biogenesis Inhibition in the Murine Intestinal Epithelium

Scientists showed that ribosome biogenesis dysfunction strongly alleviated Wnt-driven tumor initiation by restoring cell cycle exit and differentiation in Apc-deficient progenitors. [Cell Death Differ] Full Article

Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction

Investigators found that aging altered epithelial immunity, metabolism, and cell proliferation and was accompanied by region-dependent skewing in the cellular composition of the epithelium. [Cell Rep] Full Article | Graphical Abstract

The Autophagy-Independent Role of BECN1 in Colorectal Cancer Metastasis through Regulating STAT3 Signaling Pathway Activation

Knockdown of BECN1 increased the phosphorylation of STAT3 and activated the STAT3 signaling pathway in colorectal cancer cells. [Cell Death Dis] Full Article

Stearoyl-CoA-Desaturase-1 Regulates Gastric Cancer Stem-Like Properties and Promotes Tumor Metastasis via Hippo/YAP Pathway

Stearoyl-CoA desaturase-1 (SCD1) was found to increase the population of gastric cancer stem cells (GCSCs), whereas its suppression by an SCD1 inhibitor or knockdown by siRNA attenuated the stemness of GCSCs, including chemotherapy resistance and sphere-forming ability. [Br J Cancer] Abstract

Bcl-3 Promotes Wnt Signaling by Maintaining the Acetylation of β-Catenin at Lysine 49 in Colorectal Cancer

Scientists report a novel function of B-cell lymphoma 3 (Bcl-3) in maintaining colorectal cancer stem cell homeostasis by activating Wnt/β-catenin signaling. [Signal Transduct Target Ther] Full Article

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The Nano-Intestine Interaction: Understanding the Location-Oriented Effects of Engineered Nanomaterials in the Intestine

A deep understanding of nanomaterial (NM)-induced location-oriented effects (LOE) will facilitate the design of safer NMs and the development of more efficient nanomedicine for intestine-related diseases. Recent progress in this field is reviewed in order to better understand the LOE of nanomaterials. [Small] Abstract

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

Clinical Genomics Expands Strategic Relationship with Quest Diagnostics and Further Increases Momentum for Innovative First-Line Colorectal Cancer Screening Blood Test

Clinical Genomics announced key business updates related to Trident, the company’s first-line colorectal cancer screening blood test program, and its strategic alliance with Quest Diagnostic. [Clinical Genomics (GlobeNewswire, Inc.)] Press Release

Pierre Fabre Receives Positive CHMP Opinion for Braftovi^® (Encorafenib) in Combination with Cetuximab for the Treatment of Adult Patients with BRAF^V600E-mutant Metastatic Colorectal Cancer

Pierre Fabre announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion recommending approval of the indication of BRAFTOVI^® in combination with cetuximab for the treatment of adult patients with BRAF^V600E-mutant metastatic colorectal cancer who have received prior systemic therapy. [Pierre Fabre (Business Wire, Inc.)] Press Release

As COVID-19 Forces Conferences Online, Scientists Discover Upsides of Virtual Format

As the novel coronavirus outbreak shutters businesses and disrupts everyday life for billions around the globe, massive annual conferences and small society meetings alike have moved online. The new format poses numerous technical and organizational challenges, but it also offers opportunities- for reaching wider audiences, reducing the carbon footprint of meeting travel, and improving diversity and equity. [ScienceInsider] Editorial

The Pandemic’s Effects on Recruiting International STEM Trainees

Pandemic-related concerns that have arisen for science trainees-shuttered labs, research and education delays, anxiety—are applicable across the board. But international graduate students and postdocs face a suite of unique challenges that raise uncertainty about recruiting and supporting this critical group of researchers in the future. [The Scientist] Editorial

In light of COVID-19, many conferences are being cancelled or postponed. As such:

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NEW Group Leader – Cancer Biology (Northwestern University)

Research Technician – Cancer (Oklahoma Medical Research Foundation)

Postdoctoral Fellow – Cancer Development (NIH National Institute of Diabetes and Digestive and Kidney Diseases)

Postdoctoral Researcher – Translational Cancer Research (Johannes Kepler University of Linz)

PhD Student – Cancer (Danish Cancer Society Research Center)

Faculty Positions – Precision Medicine (Sun Yat-Sen University)

Postdoctoral Position – Cancer Research (The Ohio State University)

Postdoctoral Fellow – Research Scientist (Medical College of Wisconsin)

Lab Manager – Intestinal Research (Howard Hughes Medical Institute)

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

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