Intestinal Cell News Volume 5.29 | Aug 9 2019

TOP STORY

Senescence-Associated Tissue Microenvironment Promotes Colon Cancer Formation through the Secretory Factor GDF15

In in vitro and ex vivo model systems, researchers induced senescence using oxidative stress in colon fibroblasts and demonstrated that the senescent fibroblasts secreted GDF15 as an essential senescence-associated secretory phenotype factor that promoted cell proliferation, migration, and invasion in colon adenoma and colorectal cancer cell lines as well as primary colon organoids via the MAPK and PI3K signaling pathways. [Aging Cell] Full Article

(Ranked by impact factor of the journal)

Genome-Wide Mapping of DNA-Binding Sites Identifies Stemness-Related Genes as Directly Repressed Targets of SNAIL1 in Colorectal Cancer Cells

Investigators used ChIP-seq to identify genes directly regulated by SNAIL1 in colorectal adenocarcinoma cells. When comparing the genomic distribution of SNAIL1 to that of the intestinal stem cell transcription factors ASCL2 and TCF7L2, they observed a significant overlap. [Oncogene] Full Article

Avenanthramide A Triggers Potent ROS-Mediated Anti-Tumor Effects in Colorectal Cancer by Directly Targeting DDX3

The authors demonstrated that avenanthramide (AVN) treatment suppressed mitochondrial bioenergetic generation, resulting in mitochondrial swelling and increased reactive oxygen species (ROS) production. Further study indicated that AVN treatment significantly reduced DDX3 expression, an oncogenic RNA helicase highly expressed in human colorectal cancer tissues. [Cell Death Dis] Full Article

The Synergistic Effects of Oxaliplatin and Piperlongumine on Colorectal Cancer Are Mediated by Oxidative Stress

The anticancer effects of oxaliplatin combined with piperlongumine (PL), a molecule promoting reactive oxygen species generation, in colorectal cancer, were assessed. Scientists demonstrated that oxaliplatin elevated cellular ROS amounts and showed synergistic anticancer effects with PL in colorectal cancer cells. [Cell Death Dis] Full Article

PACSIN2-Dependent Apical Endocytosis Regulates the Morphology of Epithelial Microvilli

To determine if loss of endocytic machinery could explain defects in microvillar morphology, researchers examined the impact of PACSIN2 KD and endocytosis inhibition on live intestinal epithelial cells. These assays revealed that when endocytic vesicle scission failed, tubules were pulled into the cytoplasm and this, in turn, led to a membrane lifting phenomenon reminiscent of that observed in PACSIN2 KO brush borders. [Mol Biol Cell] Abstract

Colorectal Cancer Cells Respond Differentially to Autophagy Inhibition In Vivo

All studied colorectal cancer (CRC) cell lines showed high basal autophagic flux. However, only HCT116 and Caco-2/15 cells displayed regulated autophagic flux upon starvation. Knockdown of ATG5 or RAB21 had little effect on CRC cell proliferation in vitro. [Sci Rep] Full Article

Stoichiogenomics Reveal Oxygen Usage Bias, Key Proteins and Pathways Associated with Stomach Cancer

Compared the oxygen and carbon contents between proteomes of stomach cancer stomach glandular cells. Key proteins, genome locations, pathways, and functional dissection associated with stomach cancer were also studied. An association of oxygen content protein expression level was revealed in stomach cancer and stomach glandular cells. [Sci Rep] Full Article

Extracellular Glutamate-Induced mTORC1 Activation via the IR/IRS/PI3K/Akt Pathway Enhances the Expansion of Porcine Intestinal Stem Cells

Investigators showed that extracellular Glu promoted intestinal stem cell expansion, indicated by increased intestinal organoid forming efficiency and budding efficiency as well as cell proliferation marker Ki67 immunofluorescence and differentiation marker Keratin 20 expression. Moreover, the insulin receptor (IR) mediating phosphorylation of the insulin receptor substrate (IRS) and downstream signaling phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was involved in this response in ISCs. [J Agric Food Chem] Abstract

Calcium-Sensing Receptor Antagonist NPS-2143 Suppresses Proliferation and Invasion of Gastric Cancer Cells

Scientists investigated the expression of calcium-sensing receptor in gastric cancer (GC) tissues using immunohistochemistry and western blotting. Then Cell Counting Kit-8 and colony formation assays were conducted to explore the effect of the NPS-2143 on the proliferation of GC cell line AGS. [Cancer Gene Ther] Abstract

The Effects of Tramadol on Cancer Stem Cells and Metabolic Changes in Colon Carcinoma Cells Lines

Scientists used Colo320, Colo741 and HCT116 colon cancer cell lines. CD133 was considered a colon cancer stem cell marker and used to sort CD133⁺ and CD133⁻ cells by magnetic cell sorting. [Gene] Abstract

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Epigenetic Biomarkers in Colorectal Cancer Patients Receiving Adjuvant or Neoadjuvant Therapy: A Systematic Review of Epidemiological Studies

The authors provide a systematic review of epidemiological studies investigating epigenetic biomarkers in colorectal cancer (CRC) patients receiving neoadjuvant or adjuvant therapy, and their potential role for the prediction of outcomes and response to treatment. They identify several epigenetic markers in CRC patients who received surgery with adjuvant or neoadjuvant therapy. [Int J Mol Sci] Full Article

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

CytoDyn Files a Phase II Protocol with the FDA for Leronlimab (PRO 140) and Regorafenib as a Combination Therapy for Metastatic Colorectal Cancer

CytoDyn Inc. announced the filing of a Phase II protocol with the FDA for a combination therapy of leronlimab and Regorafenib in patients with metastatic colorectal cancer. [CytoDyn] Press Release

Crohn’s and Colitis Canada Provides over $2.8 Million in 2019 Research Grants

Crohn’s and Colitis Canada, one of the world’s leading non-governmental funders of Crohn’s disease and ulcerative colitis research, announces over $2.8 million in grants to eleven Canadian investigators and their teams. These annual research grants, which are funded entirely by donors, fuel the most promising projects to deliver new therapeutic hope for the 270,000 Canadians living with Crohn’s disease and ulcerative colitis, the two main forms of inflammatory bowel disease. [Crohn’s and Colitis Canada (GlobeNewswire, Inc.)] Press Release

Dr. Tamara Zietek discusses the use of intestinal organoids as a model system for nutrient transport. Listen Now

UK Announces Fast-Track Visa to Recruit Top Scientists

British Prime Minister Boris Johnson has announced a new fast-track visa to attract elite scientists to live and work in the UK, in light of the nation leaving the European Union later this year. “I want the UK to continue to be a global science superpower, and when we leave the EU we will support science and research and ensure that, far from losing out, the scientific community has a huge opportunity to develop and export our innovation around the world,” Johnson said in a statement. [The Scientist] Editorial

UC Faculty Protest Elsevier by Suspending Work for Cell Press

Faculty members at a number of University of California (UC) schools have stopped serving on the editorial boards of journals published by Cell Press in protest of its parent company, Elsevier, not having reached a deal with UC for access to its publications. The 31 signatories of a letter to Elsevier, posted August 7^th online, write that unless Elsevier and UC can agree upon a new contract, they will not serve on the boards of Cell, Neuron, Immunity, Current Biology, and others. [The Scientist] Editorial

Mexican Science Suffers under Debilitating Budget Cuts

Austerity measures recently enacted by Mexico’s president are pushing the country’s scientific efforts — chronically underfunded for years — to a breaking point, according to researchers. [Nature News] Editorial

Novartis CEO: ‘We Tried to Do the Right Things’ in FDA Data Scandal

Novartis CEO Vas Narasimhan defended his company’s decision to wait three months to tell authorities about falsified data submitted to the FDA, saying the company “tried to do the right things” in the process. He also said Novartis was now “in the process of exiting” a small number of scientists at AveXis, Novartis’s gene therapy business, who were “involved in these data inaccuracies.” [STAT News] Editorial

NEW 2019 National Cancer Research Institute Cancer Conference
November 3-5, 2019
Glasgow, United Kingdom

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

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

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

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

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

Postdoctoral Fellow – Designer Probiotics (Massacheusetts General Hospital)

Postdoctoral Fellow – Multi-Omics in Intra-Tumor Heteregenity (The Institute of Cancer Research)

Postdoctoral Researchers – Microbiota in Neonatal Immunity and Imprinting (Institut Pasteur)

Postdoctoral Fellowship – Cancer Biology (Ninewells Hospital and Medical School)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

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

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