Intestinal Cell News Volume 4.25 | Jul 6 2018

TOP STORY

Optimized Base Editors Enable Efficient Editing in Cells, Organoids and Mice

The authors reengineered the sequences of BE3, BE4Gam, and xBE3 by codon optimization and incorporation of additional nuclear-localization sequences. The reengineered base editors enabled target modification in a wide range of mouse and human cell lines, and intestinal organoids. [Nat Biotechnol] Abstract

(Ranked by impact factor of the journal)

Deficiency in Class III PI3-Kinase Confers Postnatal Lethality with IBD-Like Features in Zebrafish

Scientists report that class III PI3-kinase (PIK3C3) deficiency in zebrafish results in intestinal injury and inflammation. [Nat Commun] Full Article

Zyxin Promotes Colon Cancer Tumorigenesis in a Mitotic Phosphorylation-Dependent Manner and through CDK8-Mediated YAP Activation

Depletion of zyxin resulted in significantly impaired colon cancer cell proliferation, migration, anchorage-independent growth, and tumor formation in xenograft animal models. [Proc Natl Acad Sci USA] Abstract

Nano‐TiO₂ Drives Epithelial-Mesenchymal Transition in Intestinal Epithelial Cancer Cells

Scientists showed that titanium dioxide nanoparticles (nano‐TiO₂), a common food additive, can induce the epithelial‐to‐mesenchymal transition (EMT) process in colorectal cancer cells. Nano‐TiO₂ exposure was observed to activate transforming growth factor‐β/mitogen‐activated protein kinase and wingless pathways, and drive the EMT process. [Small] Abstract

Uncoupling Hepatic Oxidative Phosphorylation Reduces Tumor Growth in Two Murine Models of Colon Cancer

The authors confirmed that diet-induced obesity promotes tumor growth in two murine colon cancer models and showed that this effect is reversed by an orally administered controlled-release mitochondrial protonophore that acts as a liver-specific uncoupler of oxidative phosphorylation. [Cell Rep] Full Article | Graphical Abstract

Alternative NF-κB Signaling Promotes Colorectal Tumorigenesis through Transcriptionally Upregulating Bcl-3

Researchers found aberrant constitutive activation of alternative NF-κB signaling both in colorectal cancer (CRC) tissue and CRC cells. [Oncogene] Abstract

A Novel lncRNA, LINC00460 Affects Cell Proliferation and Apoptosis by Regulating KLF2 and CUL4A Expression in Colorectal Cancer

Investigators found that a novel lncRNA, LINC00460, whose expression was significantly up-regulated in colorectal cancer (CRC) tissues compared to adjacent normal tissues. Consistently, qRT-PCR results also verified that LINC00460 was over-expressed in CRC tissues and cells. [Mol Ther Nucleic Acids] Abstract | Full Article

Thrombin Modifies Growth, Proliferation and Apoptosis of Human Colon Organoids: A PAR1‐ and PAR4‐Dependent Mechanism

Thrombin favored organoid maturation leading to a decreased number of immature cystic structures and a concomitant increased number of larger structures releasing cell debris and apoptotic cells. [Br J Pharmacol] Abstract

PIK3CA Mutations Confer Resistance to First-Line Chemotherapy in Colorectal Cancer

PIK3A mutation tumor cells showed poor sensitivity to first-line chemotherapy in vitro and in vivo. PIK3CA mutation induced PI3K/Akt signaling activation to increase LGR5⁺ colorectal cancer stem cells survival and proliferation, from which lead to chemotherapy resistance. [Cell Death Dis] Full Article

Imbalanced LIMK1 and LIMK2 Expression Leads to Human Colorectal Cancer Progression and Metastasis via Promoting β-Catenin Nuclear Translocation

Researchers identified that LIM domain kinase (LIMK)2 was progressively downregulated with tumor progression from precancerous lesions to advanced cancer. Gain- and loss-of-function assays revealed that LIMK2 inhibits cell proliferation via cell cycle arrest at the G1-S transition and suppresses the ability of cell metastasis by restricting the epithelial–mesenchymal transition process. [Cell Death Dis] Full Article

The Stress Response Gene ATF3 Is a Direct Target of the Wnt/β-Catenin Pathway and Inhibits the Invasion and Migration of HCT116 Human Colorectal Cancer Cells

Investigators showed that the stress response gene ATF3 is transcriptionally activated by the binding of β-catenin and TCF4 to the redundant TCF4 site at the proximal promoter region of the ATF3 gene, indicating that ATF3 is a direct target of the Wnt/β-catenin pathway. [PLoS One] Full Article

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Patient-Derived Tumor Organoids for Prediction of Cancer Treatment Response

The authors compare organoids with the more traditional laboratory models, such as cell lines and xenografts, and review the literature of the current role of cancer organoids in determining treatment responses. [Semin Cancer Biol] Abstract

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

£215 Million Research Fund to Tackle the Next Generation of Health Challenges

The government has announced £215 million investment in NHS health research and an additional £3 million for a new research leader program for nurses and midwives. [Gov.UK] Press Release

UH Cancer Center Renews NCI Designation

The University of Hawai‘i (UH) Cancer Center successfully competed for renewal of National Cancer Institute (NCI) designation, and has been awarded a $6 million Cancer Center Support Grant to fund research at the Center. [University of Hawai’i Cancer Center] Press Release

Dr. Jason Spence shares his insights on the derivation of organoids from hPSCs. Listen Now

Controversial CRISPR ‘Gene Drives’ Tested in Mammals for the First Time

A controversial technology capable of altering the genomes of entire species has been applied to mammals for the first time. In a preprint posted to bioRxiv on 4 July, researchers describe developing ‘gene drives’ — which could be used to eradicate problematic animal populations — in lab mice using the CRISPR gene-editing technique. [Nature News] Editorial

China’s Scientific Revolution

The country is making a serious investment in becoming a world-class science superpower. [Scientific American] Editorial

Hidden Conflicts? Pharma Payments to FDA Advisers after Drug Approvals Spark Ethical Concerns

In examining compensation records from drug companies to physicians who advised FDA on whether to approve 28 psychopharmacologic, arthritis, and cardiac or renal drugs between 2008 and 2014, Science found widespread after-the-fact payments or research support to panel members. The agency’s safeguards against potential conflicts of interest are not designed to prevent such future financial ties. [ScienceInsider] Editorial

Hungarian Academy to Draw Up Alternative Research Budget

The Hungarian Academy of Sciences is set to put forward an “alternative proposal” for the country’s research budget, after the government moved to put the Ministry of Innovation and Technology in charge of financing research institutions, seen as the latest attack on sector autonomy by the authoritarian Orbán administration. [Times Higher Education] Editorial

NEW Cell Symposia: Translation of Stem Cells to the Clinic: Challenges and Opportunities
December 2-4, 2018
Los Angeles, California, United States

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

NEW Postdoctoral Scholar – Molecular and Cell Biology (University of California, Berkeley)

Assistant Professor – Cancer Biology (Université de Genève)

Postdoctoral Research Position – Cancer Biology (Medical Research Council)

Postdoctoral Fellow – Colorectal Cancer (Dalhousie University)

PhD position – Inflammatory Bowel Disease (Universitätsmedizin Berlin)

Postdoctoral Fellow Position – Intestinal Research (Vanderbilt University Medical Center)

Postdoctoral Position – Cancer Biology and Metastasis (MD Anderson Cancer Center)

Associate/Full Researcher – Cancer Biology (University of Hawaii Cancer Center)

Postdoctoral Positions – Colon Stem Cells and Carcinogenesis (Johns Hopkins University School of Medicine)

Postdoctoral Fellowship – Inflammatory Bowel Disease (European Molecular Biology Laboratory)

Postdoctoral Position – Digestive Health (University of California, Irvine)

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