Intestinal Cell News Volume 5.42 | Nov 8 2019

TOP STORY

Adaptive Mutability of Colorectal Cancers in Response to Targeted Therapies

Researchers investigated whether human colorectal cancer cells exploited adaptive mutability to evade therapeutic pressure. They found that epidermal growth factor receptor (EGFR)/BRAF inhibition down-regulated mismatch repair and homologous recombination DNA repair genes, and concomitantly up-regulated error-prone polymerases in drug-tolerant cells. [Science] Abstract | Editorial

(Ranked by impact factor of the journal)

Long-Term Culture Captures Injury-Repair Cycles of Colonic Stem Cells

Investigators identified a Hopx⁺ colitis-associated regenerative stem cell population that functionally contributed to mucosal repair in mouse models of colitis. Hopx⁺ CARSCs, enriched for fetal-like markers, transiently arose from hypertrophic crypts known to facilitate regeneration. [Cell] Full Article | Graphical Abstract

A MYC-GCN2-eIF2α Negative Feedback Loop Limits Protein Synthesis to Prevent MYC-Dependent Apoptosis in Colorectal Cancer

Depletion of eIF2B5 induced an integrated stress response and enhanced translation of MYC via an internal ribosomal entry site. This perturbed cellular amino acid and nucleotide pools, strained energy resources and caused MYC-dependent apoptosis. [Nat Cell Biol] Abstract

Asymmetric Distribution of TLR3 Leads to a Polarized Immune Response in Human Intestinal Epithelial Cells

Using primary human intestinal epithelial cells (IECs), investigators probed the mechanisms that allow for such a tolerance. They discovered that viral infections emanating from the basolateral side of IECs elicited a stronger intrinsic immune response in comparison to lumenal apical infections. [Nat Microbiol] Abstract

MRTFB Suppresses Colorectal Cancer Development through Regulating SPDL1 and MCAM

Using a combination of cell-based assays, in vivo tumor xenograft assays, and myocardin-related transcription factor B (Mrtfb) knockout mice, researchers demonstrated that MRTFB was a human and mouse colorectal cancer tumor suppressor that functioned in part by inhibiting cell invasion and migration. To identify possible MRTFB transcriptional targets, they performed whole transcriptome RNA sequencing in MRTFB siRNA knockdown primary human colon cells and identified 15 differentially expressed genes. [Proc Natl Acad Sci USA] Abstract

Organoids Reveal That Inherent Radiosensitivity of Small and Large Intestinal Stem Cells Determines Organ Sensitivity

The authors established a protocol for irradiating organoids that delivered radiation profiles simulating the organ of origin. This technique yielded highly similar dose survival curves of small and large intestinal crypts in vivo and their cognate organoids analyzed by the single hit multi-target algorithm, outcomes reflecting the inherent radiation profile of their respective Lgr5⁺ stem cell populations. [Cancer Res] Abstract

Cannabidiol Promotes Apoptosis via Regulation of XIAP/Smac in Gastric Cancer

Cannabidiol (CBD) promoted cell death in gastric cancer. The authors suggested that CBD induced apoptosis by suppressing X-linked inhibitor apoptosis (XIAP), a member of the IAP protein family. CBD reduced XIAP protein levels while increasing ubiquitination of XIAP. [Cell Death Dis] Full Article

MKK3 Sustains Cell Proliferation and Survival through p38DELTA MAPK Activation in Colorectal Cancer

Scientists retrospectively explored the prognostic and pathobiologic relevance of mitogen-activated protein kinase-kinase 3 (MKK3) in a cohort of colorectal cancer (CRC) patients and assessed MKK3 molecular functions in a panel of CRC lines and colonocytes primary cultures. They found increased MKK3 levels in late-stage CRC patients which correlated with shorter overall survival. [Cell Death Dis] Full Article

Extracellular Vesicles Transmit Epithelial Growth Factor Activity in the Intestinal Stem Cell Niche

By using 3D mouse and human intestinal organoids, scientists showed that intestinal fibroblast-derived extracellular vesicles (EVs) were involved in forming the intestinal stem cell population (ISC) niche by transmitting Wnt and epidermal growth factor (EGF) activity. With a mouse model that expressed EGFP in the Lgr5⁺ ISCs the authors proved that loss in ISC number in the absence of EGF was prevented by fibroblast-derived EVs. [Stem Cells] Abstract

Visualization of Epithelial-Mesenchymal Transition in an Inflammatory Microenvironment-Colorectal Cancer Network

Scientists showed the spatiotemporal visualization of colorectal cancer cells (CRC) cells undergoing epithelial-to-mesenchymal transition (EMT) using a fluorescence-guided EMT imaging system in which the mesenchymal vimentin promoter drove red fluorescent protein (RFP) expression. An inflammatory microenvironment including TNF-α, IL-1β, and cytokine-secreting inflammatory macrophages induced RFP expression in association with the EMT phenotype in CRC cells. [Sci Rep] Full Article

Phosphoproteomics Enables Molecular Subtyping and Nomination of Kinase Candidates for Individual Patients of Diffuse-Type Gastric Cancer

Researchers identified 16 kinases whose activities were associated with poor overall survival. These activated kinases covered several cancer hallmark pathways with the MTOR signaling network being the most frequently activated. They proposed a patient-specific strategy based on the hierarchy of clinically actionable kinases for prioritization of kinases for further clinical evaluation. [iScience] Abstract | Graphical Abstract

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Serrated Colorectal Cancer: The Road Less Traveled?

Aggressive colorectal cancers (CRCs) harbor the characteristics of serrated tumors, suggesting that initiation through this alternative pathway determines how aggressive the CRC becomes. They authors review recent evidence on how serrated carcinogenesis contributes to the subtype of CRC with the poorest prognosis. [Trends Cancer] Abstract

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

Protein Data Bank at Rutgers Awarded $34.5 Million Grant

The RCSB Protein Data Bank headquartered at Rutgers University-New Brunswick has been awarded $34.5 million in grants over five years from three US government agencies. The funding – an approximately 5% increase over the previous five-year period – covers ongoing operations and will expand the reach of the world’s only open-access, digital data resource for the 3D biomolecular structures of life. [Rutgers University-New Brunswick (EurekAlert!)] Press Release

Three UCLA Scientists Receive Grants Totaling More Than $18 Million

Three researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have received awards totaling more than $18 million from the California Institute for Regenerative Medicine, the state’s stem cell agency. [University of California – Los Angeles Health Sciences (EurekAlert!)] Press Release

Texas Voters Approve Second Life for State Cancer Funding Agency

On 5 November, Texas voters approved (64% to 36%) a ballot measure to extend the life of its pioneering state cancer research funding agency, CPRIT, by doubling, to $6 billion, the amount of bonds that can be issued to support the agency. [ScienceInsider] Editorial

Report Sketches Vision for UK Research After Brexit

An eagerly awaited external report, commissioned by the government, lays out research priorities and options if those relationships with Europe are severed. It calls for increased spending on R&D nationwide, a new research fellowship program, and larger chunks of money for universities to quickly target research opportunities. [ScienceInsider] Editorial

NEW Exosomes in Human Infectious Diseases Conference
March 5-8, 2020
Nassau, Bahamas

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

NEW Postdoctoral Researcher – Mucosal Immunology (KU Leuven)

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

PhD Student – Gut Microbiota on Intestinal Inflammation (Flanders Institute for Biotechnology)

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)

Assistant Professors – Microbiome Research (University of Illinois at Urbana-Champaign)

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)

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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