Extracellular signal-regulated kinase 5 increases radioresistance of lung cancer cells by enhancing the DNA damage response

Experimental & Molecular Medicine
Weiwei JiangZi-Chun Hua

Abstract

Radiotherapy is a frequent mode of cancer treatment, although the development of radioresistance limits its effectiveness. Extensive investigations indicate the diversity of the mechanisms underlying radioresistance. Here, we aimed to explore the effects of extracellular signal-regulated kinase 5 (ERK5) on lung cancer radioresistance and the associated mechanisms. Our data showed that ERK5 is activated during solid lung cancer development, and ectopic expression of ERK5 promoted cell proliferation and G2/M cell cycle transition. In addition, we found that ERK5 is a potential regulator of radiosensitivity in lung cancer cells. Mechanistic investigations revealed that ERK5 could trigger IR-induced activation of Chk1, which has been implicated in DNA repair and cell cycle arrest in response to DNA double-strand breaks (DSBs). Subsequently, ERK5 knockdown or pharmacological inhibition selectively inhibited colony formation of lung cancer cells and enhanced IR-induced G2/M arrest and apoptosis. In vivo, ERK5 knockdown strongly radiosensitized A549 and LLC tumor xenografts to inhibition, with a higher apoptotic response and reduced tumor neovascularization. Taken together, our data indicate that ERK5 is a novel potential target for t...Continue Reading

References

Oct 26, 1999·The Journal of Biological Chemistry·J M EnglishM H Cobb
Jun 14, 2000·Immunologic Research·Y KatoJ D Lee
Mar 10, 2001·Nature·L Chang, M Karin
Dec 12, 2001·Molecular and Cellular Biology·Azucena Esparís-OgandoAtanasio Pandiella
Jul 3, 2002·Proceedings of the National Academy of Sciences of the United States of America·Christopher P ReganKeisuke Kuida
Jul 5, 2003·Molecular and Cellular Biochemistry·Tána RavingerováMonika Strnisková
Aug 23, 2003·Oncogene·Roseann MulloyRobert A Hipskind
Jun 11, 2004·Annual Review of Biochemistry·Aziz SancarStuart Linn
Jul 6, 2004·International Journal of Radiation Oncology, Biology, Physics·Timothy M Pawlik, Khandan Keyomarsi
Dec 6, 2005·Nature Cell Biology·Ali JazayeriStephen P Jackson
Dec 27, 2005·Cellular Signalling·Xin Wang, Cathy Tournier
Jan 25, 2006·The Journal of Biological Chemistry·Jeremy S Myers, David Cortez
Aug 2, 2006·EMBO Reports·Satoko Nishimoto, Eisuke Nishida
Feb 8, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Shufeng LiZi-Chun Hua
Apr 25, 2007·The Journal of Cell Biology·Kelly CudeZhengui Xia
Jul 31, 2007·Cell Cycle·Graham Dellaire, David P Bazett-Jones
Aug 8, 2007·International Journal of Cancer. Journal International Du Cancer·Guang-Hui JinZi-Chun Hua
Sep 2, 2008·The Lancet Oncology·Justin A CallD Ross Camidge
Sep 6, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Hongqin ZhuangZi-Chun Hua
Apr 25, 2013·International Journal of Cancer. Journal International Du Cancer·Youwei Zhang, Tony Hunter
Sep 13, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Liufu DengYang-Xin Fu
Jan 9, 2016·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Feb 6, 2017·Cancer Letters·Van T HoangMatthew E Burow
Jul 20, 2018·Therapeutic Advances in Medical Oncology·Anna MinchomJuanita Lopez

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Methods Mentioned

BETA
transfection
transfections
fluorescence microscopy
flow cytometry
enzyme-linked immunosorbent assay
ELISA
Assay
xenograft
X-ray
PCR

Software Mentioned

GraphPad Prism -
CellQuest
ImageJ
SPSS
GraphPad Prism

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