Hepatic Cell News Volume 4.03 | Jan 31 2020

TOP STORY

The Tight Junction Protein TJP1 Regulates the Feeding-Modulated Hepatic Circadian Clock

Researchers showed that tight junction protein 1 (TJP1) functioned as a mediator of mechanistic target of rapamycin (mTOR) to modulate the hepatic circadian clock. TJP1 interacted with PER1 and prevented its nuclear translocation. During feeding, mTOR phosphorylated TJP1 and attenuated its association with PER1, thereby enhancing nuclear shuttling of PER1 to dampen circadian oscillation. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Smad Phospho-Isoforms for Hepatocellular Carcinoma Risk Assessment in Patients with Nonalcoholic Steatohepatitis

Investigators immunohistochemically examined domain-specific Smad3 phosphorylation in liver biopsy specimens from 30 nonalcoholic steatohepatiti (NASH) patients representing different fibrotic stages and 20 chronically infected hepatitis C patients as controls, correlating Smad3 phosphorylation with clinical course. Hepatocellualer carcinoma occurred during follow-up in 11 of 12 NASH patients with abundant pSmad3L and limited pSmad3C but in only 2 of 18 with limited pSmad3L. [Cancers] Abstract | Download Full Article

The Critical Role of Glucose Deprivation in Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma under Hypoxia

The authors hypothesized that metastasis was likely attributable to the complexity and heterogeneity of the cancer microenvironment. To identify the cancer microenvironment that induced the epithelial-mesenchymal transition (EMT) process, tumor areas of patients with hepatoceullar carcinoma were analyzed by immunostaining. [Sci Rep] Full Article

Arabinogalactan Derived From Lycium barbarum Fruit Inhibits Cancer Cell Growth via Cell Cycle Arrest and Apoptosis

Scientists compared the effects of L. barbarum fruit polysaccharide fractions on the growth of hepatoma cells, cervical cancer cells, gastric carcinoma cells, and human breast cancer cells. LBGP-I-3 showed stronger inhibitory effects on MCF-7 cells than SMMC-7721 and HeLa cells, and had no effect on HepG2 and SGC-7901 cells. [Int J Biol Macromol] Abstract

Sesamol Alleviates Obesity-Related Hepatic Steatosis via Activating Hepatic PKA Pathway

Sesamol (SEM) activated AMP-activated protein kinase, which might explain the regulatory effect of SEM on fatty acid β-oxidation and lipogenesis. Additionally, the protein kinase A (PKA-C) and phospho-PKA substrate levels were higher after SEM treatment. [Nutrients] Abstract | Download Full Article | Graphical Abstract

The Long-Noncoding RNA MALAT1 Regulates TGF-β/Smad Signaling through Formation of a lncRNA-Protein Complex with Smads, SETD2 and PPM1A in Hepatic Cells

Investigators showed that the lncRNA MALAT1 protein complex facilitated the dephosphorylation of pSmad2/3 by providing the interaction niche for pSmad2/3 and their specific phosphatase PPM1A, thus terminating TGF-β/Smad signaling in hepatic cells. [PLoS One] Full Article

MiR-23a-3p Promoted G1/S Cell Cycle Transition by Targeting protocadherin17 in Hepatocellular Carcinoma

The authors evaluating the effects of miR-23a-3p and protocadherin17 (PCDH17) on hepatocellular carcinoma (HCC) cell cycle and underlining the mechanism. The level of miR-23a-3p was up-regulated, while PCDH17 level was down–egulated in HCC tissues compared to adjacent tissues. [J Physiol Biochem] Abstract

Gross Type of Hepatocellular Carcinoma Reflects the Tumor Hypoxia, Fibrosis, and Stemness-Related Marker Expression

The histopathological features, clinical outcomes of hepatocellular carcinoma (HCC) gross types, and their relationships with stemness-related marker status and fibrotic/hypoxic tumor microenvironment were evaluated in 266 resected HCCs. The stemness-related markers, fibrous tumor stroma, and hypoxia were evaluated with immunohistochemistry. [Hepatol Int] Abstract

Dynamic Changes in Function and Proteomic Composition of Extracellular Vesicles from Hepatic Stellate Cells During Cellular Activation

Extracellular vesicle (EVs) from day four mHSC contained only 46 proteins in which histones and keratins predominated, while EVs from passage 1 mHSC contained 337 proteins and these were principally associated with extracellular spaces or matrix, proteasome, collagens, vesicular transport, metabolic enzymes, ribosomes and chaperones. [Cells] Abstract | Download Full Article

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Extracellular Vesicles, a Possible Theranostic Platform Strategy for Hepatocellular Carcinoma-an Overview

The measurement and modification of extracellular vesicle (EVs) cargoes-composed of nucleic acids, including miRNAs, proteins, and lipids-holds great promise for future hepatocellular carcinoma (HCC) diagnosis, prognosis, and treatment. The authors provide an overview of the most recent findings regarding EVs in HCC, and the possible future use of EVs as “liquid biopsy”-based biomarkers for early diagnosis and as a vehicle for targeted drug-delivery. [Cancers] Abstract

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

Genentech Submits Supplemental Biologics License Application to the FDA for Tecentriq in Combination with Avastin for the Most Common Form of Liver Cancer

Genentech, a member of the Roche Group announced the completion of a supplemental Biologics License Application submission to the FDA for Tecentriq^® in combination with Avastin^® for the treatment of people with unresectable hepatocellular carcinoma who have not received prior systemic therapy. [Genentech] Press Release

Alnylam Receives Positive CHMP Opinion for GIVLAARI™ (Givosiran) for the Treatment of Acute Hepatic Porphyria in Adults and Adolescents

Alnylam Pharmaceuticals, Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending approval of givosiran, an RNAi therapeutic targeting aminolevulinic acid synthase 1 for the treatment of acute hepatic porphyria in adults and adolescents aged 12 years and older. [Alnylam Pharmaceuticals, Inc.] Press Release

Exelixis Announces Partner Takeda Files New Drug Application in Japan for CABOMETYX® (Cabozantinib) for Advanced Hepatocellular Carcinoma

Exelixis, Inc. announced that Takeda Pharmaceutical Company Limited, its partner responsible for the clinical development and commercialization of CABOMETYX^® in Japan, has applied to the Japanese Ministry of Health, Labor and Welfare for Manufacturing and Marketing Approval of cabozantinib as a treatment for patients with unresectable hepatocellular carcinoma that had progressed after prior systemic therapy. [Exelixis, Inc.] Press Release

Scripps Acquires Pfizer’s Massive Microbial Library

The East Coast campus of the research institute received shipments of freeze-dried or frozen samples of more than 210,000 microbial strains, which scientists plan to mine for potentially useful natural products. [The Scientist] Editorial

Will Elizabeth Warren’s Stance against “Junk Science” Matter to Voters?

Senator Elizabeth Warren of Massachusetts has come out with a proposal to keep so-called junk science, supported by industry, out of federal policy decisions. Many scientists have pointed out that misleading research and evidence, raised to new prominence under the Trump administration, has led to environmental and health policies that endanger the public. The coming week may tell whether Warren’s approach resonates with people in a bellwether state. [Scientific American] Editorial

NEW American Association for Cancer Research (AACR) Meeting: The Evolving Landscape of Cancer Modeling
March 2-5, 2020
San Diego, California, United States

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

NEW Postdoctoral Fellow – Diabetes and Fatty Liver Disease (NIH National Heart, Lung, and Blood Institute)

Postdoctoral Position – Culturing ‘Foie Gras’ (KU Leuven)

Team Leader – Cholangiocytes (Miromatrix Medical)

Postdoctoral Fellow – Cell Therapy for Liver Repair (University of Edinburgh)

Program Leader – Propionic Acidemia Research (None)

Postdoctoral Fellow – Metabolic Dysfunction (Lewis Katz School of Medicine)

Postdoctoral Researchers – MicroRNAs in NAFLD (Weill Cornell Medicine)

Postdoctoral Fellow – Translational Cancer Research (University of New Mexico Comprehensive Cancer Center)

Research Associate – Liver Damage (University of Colorado Denver)

Postdoctoral Researcher – Cell Biology of the Liver (Max Planck Institute of Immunobiology and Epigenetics)

Postdoctoral Fellow – Liver Pathology (University of Illinois at Chicago)

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