Hepatic Cell News Volume 2.17 | May 11 2018

TOP STORY

Baicalein Targets GTPase-Mediated Autophagy to Eliminate Liver Tumor Initiating Stem Cell-Like Cells Resistant to mTORC1 Inhibition

In search for a compound which rescinds tumor initiating stem cell‐like cells (TICs) resistance to mTORC1 inhibition and improves chemotherapy, researchers identified baicalein which selectively chemosensitizes TICs and the human HCC cell line Huh7 cells but not mouse and human primary hepatocytes. [Hepatology] Abstract

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The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma

The existence and function of achaete-scute homolog-1 (ASH1)-miR-375-YWHAZ signaling axis in hepatocellular carcinoma was determined. Studies revealed that YWHAZ was involved in several protein networks, such as cell autophagy, epithelial-mesenchymal transition, apoptosis, cell cycle, invasion, and migration. [Mol Ther Nucleic Acids] Full Article

CD31 Regulates Metastasis by Inducing Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma via the ITGB1-FAK-Akt Signaling Pathway

CD31 plays roles in cell proliferation, apoptosis, migration, and cellular immunity. CD31 is also expressed on tumor cells, such as breast cancer cells and non-Hodgkin’s lymphomas, and contributes to tumor cell invasion. Scientists showed that CD31 promotes metastasis by inducing the epithelial–mesenchymal transition in hepatocellular carcinoma by up-regulating integrin β1 via the FAK/Akt signaling pathway. [Cancer Lett] Abstract

Cholesterol Inhibits Hepatocellular Carcinoma Invasion and Metastasis by Promoting CD44 Localization in Lipid Rafts

High levels of cholesterol promoted CD44 translocation into lipid rafts and attenuated CD44-Ezrin binding, which are crucial for cell migration and cancer metastasis. The suppressive effect of cholesterol on hepatocellular carcinoma metastasis was abolished by the downregulation of CD44 or its palmitoylation inhibitor, which blocked CD44 localization in lipid rafts. [Cancer Lett] Abstract

Nucleolar TRF2 Attenuated Nucleolus Stress-Induced HCC Cell-Cycle Arrest by Altering rRNA Synthesis

Investigators found that nucleolar and coiled-body phosphoprotein 1 (NOLC1), a nucleolar protein that is responsible for the nucleolus construction and rRNA synthesis, interacted with telomeric repeat-binding factor 2 (TRF2) and mediated the shuttle of TRF2 between the nucleolus and nucleus. in hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC7721, TRF2 overexpression participated in the nucleolus stress-induced rRNA inhibition and cell-cycle arrest. [Cell Death Dis] Full Article

HCC-Derived Exosomes Elicit HCC Progression and Recurrence by Epithelial-Mesenchymal Transition through MAPK/ERK Signaling Pathway

Researchers found that exosomes from highly metastatic MHCC97H cells could communicate with low metastatic hepatocellular carcinoma (HCC) cells, increasing their migration, chemotaxis and invasion. Mechanistic studies showed that the biological alterations in HCC cells treated with MHCC97H-derived exosomes or MHCC97H cells with reduced self-derived exosome secretion were caused by inducing epithelial-mesenchymal transition via MAPK/ERK signaling. [Cell Death Dis] Full Article

Curcumin Inhibits Hepatic Stellate Cell Activation via Suppression of Succinate-Associated HIF-1α Induction

In mouse primary hepatic stellate cells, curcumin prevented succinate- and CoCl₂-induced hypoxia-inducible transcription factor-1α induction via suppression of ROS production and effectively reduced gene expressions of Col1α, Col3α, fibronectin and TGF-β1 with inflammation inhibition. [Mol Cell Endocrinol] Abstract

FABP4 Suppresses Proliferation and Invasion of Hepatocellular Carcinoma Cells and Predicts a Poor Prognosis for Hepatocellular Carcinoma

Scientists revealed that adipocyte fatty acid‐binding protein (FABP4) suppressed hepatocellular carcinoma cell proliferation and invasion in vitro. Overexpression of FABP4 led to inhibitition of tumor growth and decreased tumor volume in vivo. [Cancer Med] Full Article

Arsenic Trioxide Induces Apoptosis and Inhibits the Growth of Human Liver Cancer Cells

A significant reduction in cell growth and viability was reported in liver cancerous cells as compared to normal cells at 5 μM arsenic trioxide (As₂O₃). As₂O₃ induced apoptosis along with down-regulation of anti-apoptotic protein Bcl-xL, and up regulated expression of Notch that led towards apoptosis. [Life Sci] Abstract

Targeting Oxidative Stress for the Treatment of Liver Fibrosis

The authors overview the role of reactive oxygen species (ROS) in liver fibrosis and discuss the promising therapeutic interventions related to oxidative stress. Novel drugs that directly target the molecular pathways responsible for ROS generation, namely, mitochondrial dysfunction inhibitors, endoplasmic reticulum stress inhibitors, NADPH oxidase inhibitors, and toll-like receptor-affecting agents, are reviewed in detail. [Rev Physiol Biochem Pharmacol] Abstract

Emerging Roles of G Protein-Coupled Receptors in Hepatocellular Carcinoma

Researchers sum up the functions of G protein-coupled receptors—particularly those coupled to chemokines, prostaglandin, lysophosphatidic acid, endothelin, catecholamine, and angiotensin—in the proliferation, invasion, metastasis, and angiogenesis of hepatoma cells and the development of hepatocellular carcinoma. [Int J Mol Sci] Full Article

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

Wave Life Sciences Highlights Progress on Hepatic Collaboration with Pfizer

Wave Life Sciences Ltd. announced that Pfizer recently nominated the fourth and fifth final hepatic targets under the collaboration agreement between the two companies to develop genetically targeted therapies for the treatment of metabolic hepatic diseases, such as nonalcoholic steatohepatitis. [Wave Life Sciences Ltd.] Press Release

CymaBay Therapeutics Announces the Initiation of a Phase IIb Study of Seladelpar in Patients with Non-Alcoholic Steatohepatitis

CymaBay Therapeutics, Inc. announced that it began screening of patients for a Phase IIb proof of concept study of seladelpar for the treatment of non-alcoholic steatohepatitis. [CymaBay Therapeutics, Inc.] Press Release

Delcath Announces Initiation of Registrational Trial of Melphalan/HDS in Intrahepatic Cholangiocarcinoma

Delcath Systems, Inc. announced that the company has initiated its pivotal trial of Melphalan Hydrochloride for Injection for use with the Delcath Hepatic Delivery System (Melphalan/HDS) to treat patients with intrahepatic cholangiocarcinoma. [Delcath Systems, Inc.] Press Release

FDA Seeks Permanent Injunctions against Two Stem Cell Clinics

The FDA, in two complaints filed in federal court, is seeking permanent injunctions to stop two stem cell clinics from marketing stem cell products without FDA approval and for significant deviations from current good manufacturing practice requirements. [U.S. Food and Drug Administration] Press Release

Hungarian Scientists Are on Edge As Country Is Poised to Force Out Top University

In early April, several days after Viktor Orbán secured his third consecutive term—and fourth overall—as Hungarian prime minister with a landslide victory for his conservative party, the pro-government paper Figyelő; published a list of more than 200 people it called “mercenaries” of George Soros, the American-Hungarian billionaire philanthropist. The list included investigative journalists and human rights advocates—and 30 academics from the Soros-founded, Budapest-based Central European University. [ScienceInsider] Editorial

Australian Budget Delivers for Science Facilities and Medical Research

The government will push to invest almost Aus$1.9 billion (US$1.4 billion) over the next 12 years in shared research infrastructure — such as microscopes, supercomputers, a marine observing system and telescopes used in myriad disciplines, from nanotechnology to oceanography. Medical research will receive an increase of $1.3 billion, to be spent on various programs and initiatives over 10 years that improve health and boost the medical industry, including $500 million for a genomics and precision-medicine initiative. [Nature News] Editorial

Animal Tests Surge under New U.S. Chemical Safety Law

The cause of the increase isn’t clear. But the new law imposes stricter requirements on a broader array of chemicals than its predecessor, including both new products and ones already on the market, and experts say Environmental Protection Agency staff may be trying to comply by gathering more test data from companies. [ScienceInsider] Editorial

NEW Federation of American Societies for Experimental Biology (FASEB): Cross-Translational Research in Fibrosis across Organs
September 30-October 5, 2018
Scottsdale, Arizona, United States

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

NEW Postdoctoral Fellow – Liver Injury, Hepatocellular Carcinoma and Metabolic Liver Diseases (University of Rhode Island)

Research Technologist – Liver Biology (STEMCELL Technologies Inc.)

Postdoctoral Position – Necroptosis in Liver Diseases (Inserm)

EBPOD Fellowship – NAFLD/NASH (European Molecular Biology Laboratory)

Academic Position – Cancer Research (Cedars-Sinai Medical Center)

Postdoctoral Research Fellow – Liver Cancer Pathogenesis and Immunobiology (Fred Hutchinson Cancer Research Center)

NEW Tenure-Track Faculty Position – Cancer Research (University of Ottawa)

Postdoctoral Research Associate – Liver Disease and Injury (University of Pittsburgh)

PhD Student – Hepatology and Cancer Biology (German Cancer Research Center)

Research Fellow – Liver Tumorigenesis (Harvard School of Dental Medicine)

Postdoctoral Fellow – Alcoholic Liver Disease (University of North Carolina at Greensboro)

Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

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