Elevated hepatocyte growth factor expression as an autocrine c-Met activation mechanism in acquired resistance to sorafenib in hepatocellular carcinoma cells

Cancer Science
Zeynep Firtina KaragonlarNeşe Atabey

Abstract

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third leading cause of cancer-related deaths worldwide. Limitations in HCC treatment result due to poor prognosis and resistance against traditional radiotherapy and chemotherapies. The multikinase inhibitor sorafenib is the only FDA approved drug available for advanced HCC patients, and development of second-line treatment options for patients who cannot tolerate or develop resistance to sorafenib is an urgent medical need. In this study, we established sorafenib-resistant cells from Huh7 and Mahlavu cell lines by long-term sorafenib exposure. Sorafenib-resistant HCC cells acquired spindle-shape morphology, upregulated mesenchymal markers, and showed significant increase in both migration and invasion abilities compared to their parental counterparts. Moreover, after long-term sorafenib treatment, HCC cells showed induction of hepatocyte growth factor (HGF) synthesis and secretion along with increased levels of c-Met kinase and its active phosphorylated form, indicating autocrine activation of HGF/c-Met signaling. Importantly, the combined treatment of the resistant cells with c-Met kinase inhibitor SU11274 and HGF neutralizing antibody sign...Continue Reading

References

Dec 20, 2003·Nature Reviews. Molecular Cell Biology·Carmen BirchmeierGeorge F Vande Woude
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Chang-Goo HuhSnorri S Thorgeirsson
Jul 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Malgorzata BorowiakCarmen Birchmeier
May 20, 2006·The Journal of Clinical Investigation·Pal Kaposi-NovakSnorri S Thorgeirsson
Dec 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·James BeanWilliam Pao
Apr 9, 2008·The Cancer Journal·Melanie B Thomas
Jul 25, 2008·The New England Journal of Medicine·Josep M LlovetUNKNOWN SHARP Investigators Study Group
Dec 5, 2008·The New England Journal of Medicine·Giancarlo Spinzi, Silvia Paggi
Jan 7, 2009·International Journal of Cancer. Journal International Du Cancer·Philip Marx-StoeltingMichael Schwarz
Feb 5, 2010·Cancer Cell·Alexa B TurkePasi A Jänne
Mar 23, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Fabiola CecchiDonald P Bottaro
Nov 26, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David LiskaMartin R Weiser
Nov 26, 2010·Nature Reviews. Molecular Cell Biology·Livio TrusolinoPaolo M Comoglio
Jan 6, 2011·The Journal of Pharmacology and Experimental Therapeutics·Kuen-Feng ChenAnn-Lii Cheng
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Nov 5, 2011·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Seiji YanoMasayuki Noguchi
Dec 1, 2011·Therapeutic Advances in Medical Oncology·Shawna Leslie Organ, Ming-Sound Tsao
Dec 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Qian XieGeorge F Vande Woude
Jan 6, 2012·International Journal of Clinical Oncology·Shunsuke KondoTakuji Okusaka
Feb 23, 2012·Lancet·Alejandro FornerJordi Bruix
Feb 23, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Augusto Villanueva, Josep M Llovet
Jun 12, 2012·Nature Medicine·Alex KentsisA Thomas Look
Nov 14, 2012·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Angela Gauthier, Mitchell Ho
Nov 14, 2012·Nature Reviews. Gastroenterology & Hepatology·Augusto VillanuevaJosep M Llovet
Jun 19, 2013·The Journal of Surgical Research·Roberto GedalyB Mark Evers
Nov 2, 2013·Therapeutic Advances in Gastroenterology·A Ruth He, Alec S Goldenberg
Nov 29, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Israel CañadasEdurne Arriola
Jan 5, 2014·Pharmacology & Therapeutics·Christiane R Maroun, Tracey Rowlands
Apr 5, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Qingfeng XiangYajin Chen

❮ Previous
Next ❯

Citations

May 1, 2016·Journal of Hepatology·Andrew X ZhuDerek Y Chiang
May 2, 2016·Biochemical and Biophysical Research Communications·Zeynep Firtina KaragonlarEsra Erdal
Aug 12, 2016·Targeted Oncology·Supritha G SwamyAnupam Bishayee
Dec 6, 2016·Scientific Reports·Ha-Jeong KimDuk-Soo Bae
Jul 5, 2018·The New England Journal of Medicine·Ghassan K Abou-AlfaRobin K Kelley
Nov 8, 2018·Journal of Gastroenterology and Hepatology·Takuya AdachiUNKNOWN Okayama Liver Cancer Group
Jul 24, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Maximilian A ArdeltJohanna Pachmayr
Oct 13, 2017·The Journal of Pharmacology and Experimental Therapeutics·Qingyu ZhouRiya Choksi
Oct 23, 2019·Journal of Pharmacokinetics and Pharmacodynamics·Linh NguyenSteven Lacy
May 21, 2020·Liver International : Official Journal of the International Association for the Study of the Liver·Lorenza Rimassa, Marcus-Alexander Wörns
Apr 3, 2020·International Journal of Oncology·Yu-Xue GaoDe-Xi Chen
Jul 21, 2020·Journal of Cellular and Molecular Medicine·Evangelos KoustasAthanasios G Papavassiliou
Sep 4, 2020·Biological & Pharmaceutical Bulletin·Kojiro KobayashiYoshinori Igarashi
Aug 19, 2017·Journal of Gastrointestinal Cancer·Yeliz YılmazNeşe Atabey
Nov 19, 2019·Oxidative Medicine and Cellular Longevity·Lian-Jiu SuZhi-Yong Peng
Dec 4, 2019·Nature Reviews. Gastroenterology & Hepatology·Amanda J CraigAugusto Villanueva
Oct 31, 2019·World Journal of Gastrointestinal Oncology·Nicola PersoneniLorenza Rimassa
Oct 12, 2019·Expert Review of Anticancer Therapy·Nicola PersoneniArmando Santoro
Mar 7, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Elliot B LevyHala R Makhlouf
Jul 2, 2020·Journal of Hepatocellular Carcinoma·Audrey Debaillon VesqueJean-Frédéric Blanc
Dec 16, 2016·Journal of Cell Communication and Signaling·Evin İşcanNeşe Atabey
May 12, 2018·Molecular Medicine Reports·Shu-Lan SunHaozhe Piao
Mar 3, 2020·Frontiers in Cell and Developmental Biology·Haiyu WangZujiang Yu
Dec 9, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yuta MyojinTetsuo Takehara
Apr 8, 2021·Journal of Hepatocellular Carcinoma·Antonio D'AlessioLorenza Rimassa
May 25, 2021·Cancer Treatment Reviews·Anthony B El-KhoueiryRobin Kate Kelley

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
ELISA
fluorescence microscopy

Software Mentioned

GraphPad Prism

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis