Intestinal Cell News Volume 1.26 | Sep 18 2015

Targeting Colorectal Cancer via Its Microenvironment by Inhibiting IGF-1 Receptor-Insulin Receptor Substrate and STAT3 Signaling
Using a unique inhibitor, NT157, which targets both insulin growth factor-1 (IGF-1) and signal transducer and activator of transcription 3 (STAT3), the authors showed that these pathways regulate many tumor microenvironment functions associated with sporadic colonic tumorigenesis in CPC-APC mice, in which cancer development is driven by loss of the Apc tumor suppressor gene. [Oncogene] Abstract

PTPN11 Is a Central Node in Intrinsic and Acquired Resistance to Targeted Cancer Drugs
Researchers performed an RNA-interference-based genetic screen in BRAF mutant colon cancer cells to search for phosphatases whose knockdown induces sensitivity to BRAF inhibition. They found that suppression of protein tyrosine phosphatase non-receptor type 11 (PTPN11) confers sensitivity to BRAF inhibitors in colon cancer. [Cell Rep] Full Article | Graphical Abstract

Assessing DNA Methylation in the Developing Human Intestinal Epithelium: Potential Link to Inflammatory Bowel Disease
Scientists performed simultaneous genome-wide DNA methylation and gene expression analysis on purified intestinal epithelial cells derived from human fetal gut, healthy pediatric biopsies, and children newly diagnosed with inflammatory bowel disease. [Mucosal Immunol] Full Article

Characteristic Changes in Cell Surface Glycosylation Accompany Intestinal Epithelial Cell Differentiation: High Mannose Structures Dominate the Cell Surface Glycome of Undifferentiated Enterocytes
Nano-LC/ESI QTOF MS profiling was used to characterize the changes in glycosylation that correspond to Caco-2 cell differentiation. [Mol Cell Proteomics] Abstract | Full Article

ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer
Researchers investigated whether ERBB3 is associated with intestinal stem cell markers in colorectal cancer and if cancer stem cells within tumors are marked by expression of ERBB3. Expression of ERBB3 and intestinal stem cell markers were significantly elevated in adenomas and colorectal tumors compared to normal tissue. [PLoS One] Full Article

Upregulation of miR-582-5p Inhibits Cell Proliferation, Cell Cycle Progression and Invasion by Targeting Rab27a in Human Colorectal Carcinoma
The scientists found that microRNA (miR)-582-5p was frequently downregulated in colorectal cancer (CRC) tissues compared with corresponding noncancerous tissues, as well as in CRC cell lines. [Cancer Gene Ther] Abstract

Vitamin D Receptor-Mediated Upregulation of CYP3A4 and MDR1 by Quercetin in Caco-2 Cells
To examine whether quercetin interacts with vitamin D receptor, researchers investigated the effects of quercetin on vitamin D receptor activity in human intestinal Caco-2 cells. [Planta Med] Full Article

INTESTINAL STEM CELL & ORGANOID RESEARCH

The HSP90 Inhibitor, 17AAG, Protects the Intestinal Stem Cell Niche and Inhibits Graft versus Host Disease Development
Since the HSP90 inhibitor 17-allylamino-demethoxygeldanamycin (17AAG) is developed in clinics, investigators explored its ability to control intestinal acute graft versus host disease (GvHD) in vivo in two mouse GvHD models, ex vivo in intestine organoids and in vitro in intestinal epithelial cultures. [Oncogene] Abstract

Robust Bioengineered 3D Functional Human Intestinal Epithelium
To replicate in vitro the tissue architecture and microenvironments of native intestine, scientists developed a 3D porous protein scaffolding system, containing a geometrically-engineered hollow lumen, with adaptability to both large and small intestines. [Sci Rep] Full Article

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Cancer Research UK and MedImmune Launch Ground-Breaking Biotherapeutics Research Centre in Cambridge
A new laboratory that will focus on the discovery and development of novel biologic cancer treatments and diagnostics has been opened this week in Cambridge. The state-of-the-art CRUK-MEDI Alliance Laboratory is an innovative collaboration between Cancer Research UK, its commercial arm Cancer Research Technology, and MedImmune, the global biologics research and development arm of AstraZeneca. [Cancer Research UK] Press Release

Infinity Expands Pipeline with Addition of IPI-549, an Immuno-Oncology Development Candidate for the Treatment of Solid Tumors
Infinity Pharmaceuticals, Inc. announced the expansion of its pipeline with the addition of IPI-549, an orally administered immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase gamma, for the treatment of solid tumors. [Infinity Pharmaceuticals, Inc.] Press Release

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Research Associate – Intestinal Cell Biology (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Epigenetic Modifiers (Van Andel Research Institute)

Postdoctoral Research Fellow – Colorectal Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Drug Discovery and Action (University of Illinois)

Genetic Counselor – Cancer (Fred Hutchinson Cancer Research Center)

Harry Eagle Scholar Awards for Postdoctoral Candidates (Albert Einstein College of Medicine of Yeshiva University)

Postdoctoral Research Fellow – Ex Vivo Tumor Organoid Models (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Intestinal Immunology (Shanghai Institute of Immunology)

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