Adenovirus expressing dual c-Met-specific shRNA exhibits potent antitumor effect through autophagic cell death accompanied by senescence-like phenotypes in glioblastoma cells

Oncotarget
Jung-Sun LeeChae-Ok Yun

Abstract

c-Met, a cognate receptor tyrosine kinase of hepatocyte growth factor, is overexpressed and/or mutated in number of tumors. Therefore, abrogation of c-Met signaling may serve as potential therapeutic targets. In this study, we generated Ads expressing single shRNA specific to c-Met (shMet) (dl/shMet4 and dl/shMet5) or dual shRNAs specific to c-Met (dl/shMet4+5); and examined the therapeutic potential of these newly engineered Ads in targeting c-Met, and delineated their mechanism of action in vitro and in vivo. Ads expressing shMet induced knock-down in c-Met, and phenotypically resulted in autophagy-like features including appearance of membranousvacuoles, formation of acidic vesicular organelles, and cleavage and recruitment of microtubule-associated protein1 light chain 3 to autophagosomes. Ads expressing shMet also suppressed Akt phosphorylation and increased number of senescence-related gene products including SM22, TGase II, and PAI-1. These changes resulted in inhibition of cell proliferation and G2/M arrest of U343 cells. In vivo, intratumoral injection with dl/shMet4+5 resulted in a significant reduction of tumor growth with corresponding increasing overall survival. Histopathological analysis of these treated tumors r...Continue Reading

References

Jan 5, 2000·Genes & Development·T TuschlP A Sharp
Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·B CaoG F Vande Woude
Sep 24, 2002·Nature Biotechnology·Haibin XiaBeverly L Davidson
Nov 21, 2002·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·R L Hayward, J F Smyth
Jan 9, 2003·Expert Opinion on Investigational Drugs·A Douglas Laird, Julie M Cherrington
Jul 30, 2003·Cancer Metastasis Reviews·Patrick C MaRavi Salgia
Nov 26, 2003·The Journal of Clinical Investigation·Xueping QuBeth Levine
Dec 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Zhenyu YueNathaniel Heintz
Jul 21, 2004·Cancer Cell·Paolo MichieliPaolo M Comoglio
Nov 6, 2004·Science·Takahiro Shintani, Daniel J Klionsky
Aug 5, 2005·Nature·Manuel ColladoManuel Serrano
Aug 5, 2005·Nature·Melanie BraigClemens A Schmitt
Aug 5, 2005·Nature·Chrysiis MichaloglouDaniel S Peeper
Oct 26, 2005·Cell Death and Differentiation·N Mizushima
May 4, 2006·Journal of the National Cancer Institute·Hideaki ItoSeiji Kondo
May 25, 2006·Surgical Neurology·Shenghua ChuJie Zhang
Sep 9, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Olivier ter BrakeBen Berkhout
Jan 20, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ji Young YooChae-Ok Yun
Apr 20, 2007·The Journal of Biological Chemistry·Guillermo MariñoCarlos López-Otín
Mar 13, 2009·Genes & Development·Andrew R J YoungMasashi Narita
Aug 1, 2009·Nature Reviews. Drug Discovery·Pixu LiuJean J Zhao
Nov 30, 2012·Autophagy·Mikhail V Blagosklonny

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Citations

Nov 30, 2018·International Journal of Molecular Sciences·Cristina Trejo-SolísJulio Sotelo
Jun 9, 2021·Cell Death and Differentiation·Diane MoujalledJeffrey R Liddell
Jun 29, 2021·Frontiers in Oncology·Elisa Helena Farias JandreyÉrico Tosoni Costa
Jul 3, 2021·Cells·Don Carlo Ramos BataraSung-Hak Kim

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Methods Mentioned

BETA
xenograft
ELISA
FACS
confocal microscopy
transfection
PCR
protein assay
flow cytometry
light microscopy

Software Mentioned

FACSDiva
Stat View

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