Interleukin-6-stimulated progranulin expression contributes to the malignancy of hepatocellular carcinoma cells by activating mTOR signaling

Scientific Reports
Feng LiuYi Lu

Abstract

This study aimed to determine the expression of progranulin (PGRN) in hepatocellular carcinoma (HCC) cells in response to interleukin 6 (IL-6), a non-cellular component of the tumor microenvironment, and the molecular mechanism of PGRN oncogenic activity in hepatocarcinogenesis. Levels of IL-6 and PGRN were increased and positively correlated in HCC tissues. IL-6 dose- and time-dependently increased PGRN level in HCC cells. IL-6-driven PGRN expression was at least in part mediated by Erk/C/EBPβ signaling, and reduced expression of PGRN impaired IL-6-stimulated proliferation, migration and invasion of HepG2 cells. PGRN activated mammalian target of rapamycin (mTOR) signaling, as evidenced by increased phosphorylation of p70S6K, 4E-BP1, and Akt-Ser473/FoxO1. Inhibition of mTOR signaling with rapamycin, an mTOR signaling inhibitor, disturbed PGRN- or IL-6-mediated proliferation, migration and invasion of HCC cells in vitro. Persistent activation of mTOR signaling by knockdown of TSC2 restored PGRN-knockdown-attenuated pro-proliferation effects of IL-6 in HepG2 cells. In addition, rapamycin treatment in vivo in mice slowed tumor growth stimulated by recombinant human PGRN. Our findings provide a better understanding of the biologic...Continue Reading

References

Jul 1, 1992·Gastroenterology·H TilgC Huber
Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·T NakajimaS Akira
Oct 15, 1996·The Biochemical Journal·V BhandariA Bateman
Jun 12, 2002·Molecular Biology of the Cell·Xin ChenPatrick O Brown
Jul 4, 2002·Annals of the New York Academy of Sciences·L GiannitrapaniG Montalto
Jan 24, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Josep M Llovet, Jordi Bruix
Jun 25, 2003·The Journal of Biological Chemistry·Graciela Piwien PilipukJessica Schwartz
Aug 21, 2003·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Zhiheng He, Andrew Bateman
Feb 26, 2004·Cell·Maria Carla MottaLeonard Guarente
May 4, 2004·Nature Reviews. Cancer·Mary-Ann Bjornsti, Peter J Houghton
Oct 28, 2004·Gastroenterology·Brian I Carr
Dec 1, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Siu Tim CheungSheung Tat Fan
Dec 30, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fikret SahinMichael Torbenson
Feb 19, 2005·Science·D D SarbassovDavid M Sabatini
May 12, 2006·World Journal of Gastroenterology : WJG·Maurizio SoresiGiuseppe Montalto
Feb 27, 2007·Journal of Hepatology·David SemelaJean-François Dufour
Jun 16, 2007·Gastroenterology·Hashem B El-Serag, K Lenhard Rudolph
Oct 10, 2007·Archives of Internal Medicine·Hashem B El-SeragJames Goodwin
Oct 27, 2007·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C PortaG R Corazza
Oct 22, 2008·Gastroenterology·Augusto VillanuevaJosep M Llovet
Mar 10, 2009·International Journal of Cancer. Journal International Du Cancer·Vincent Wai-Sun WongHenry Lik-Yuen Chan
Mar 31, 2009·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Lai-Chun OngPierce K H Chow
Jul 9, 2009·International Journal of Cancer. Journal International Du Cancer·Hayato NakagawaMasao Omata
Oct 2, 2009·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Andrew Bateman, Hugh P J Bennett
Mar 23, 2010·Cell·Sergei I GrivennikovMichael Karin
Apr 23, 2010·International Immunology·Tadamitsu Kishimoto
Apr 13, 2011·Hepatology International·Sadahisa OgasawaraOsamu Yokosuka
Jun 15, 2011·Journal of Molecular Cell Biology·Ying ZhaoWei-Guo Zhu
Oct 14, 2011·The New England Journal of Medicine·Hashem B El-Serag
May 19, 2012·Cytokine & Growth Factor Reviews·Christoph GarbersJürgen Scheller
Jun 2, 2012·Cancer Treatment Reviews·Yuqi GuoZhan Zhang
Aug 10, 2012·Current Cancer Drug Targets·Laura Elisa Buitrago-Molina, Arndt Vogel
Oct 23, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Gabriel FramptonSharon DeMorrow
Jun 21, 2013·International Journal of Cancer. Journal International Du Cancer·Waka OhishiKazuaki Chayama
Jul 13, 2013·Cardiovascular Research·Ryota KawaseShizuya Yamashita
Dec 7, 2013·Journal of Hepatology·Matthias S MatterSnorri S Thorgeirsson
Dec 12, 2013·Technology in Cancer Research & Treatment·J GengM Lv

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Citations

Jun 25, 2017·Science China. Life Sciences·Shuran LiYong Yang
Jul 19, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yuanzhen SunCuimin Zou
Jan 19, 2019·Bioinformatics·Yuezhe LiPaola Vera-Licona
Aug 30, 2016·World Journal of Gastroenterology : WJG·Norio KuboKen Shirabe
Sep 25, 2017·Biochemistry. Biokhimii︠a︡·M V NovikovaP B Kopnin
Jul 25, 2019·Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry·Chunxiao LiuHongyan Wang
Apr 5, 2019·Journal of Clinical and Translational Hepatology·Shuixian DuYongning Xin
May 16, 2019·Molecular Carcinogenesis·Eunhye LeeBoyoun Park
Mar 1, 2017·Frontiers in Immunology·Yuanling LiJilong Shen
Aug 22, 2017·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yasuko YamamotoHisashi Tsurumi
Oct 19, 2016·Journal of Hepatology·Jian ShenJianping Zhang
May 1, 2021·Journal of Neurochemistry·Xiao-Ming WangQing Tian

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Methods Mentioned

BETA
acetylation
surgical resection
tissue
transfection
PCR
ELISA
flow cytometry

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