β2-AR activation induces chemoresistance by modulating p53 acetylation through upregulating Sirt1 in cervical cancer cells

Cancer Science
Hongyu ChenMing Shi

Abstract

It has been suggested that β2-adrenergic receptor (β2-AR)-mediated signaling induced by catecholamines regulates the degradation of p53. However, the underlying molecular mechanisms were not known. In the present study, we demonstrated that catecholamines upregulated the expression of silent information regulator 1 (Sirt1) through activating β2-AR-mediated signaling pathway, since selective β2-AR antagonist ICI 118, 551 and non-selective β-blocker proprenolol effectively repressed isoproterenol (ISO)-induced Sirt1 expression. Catecholamines inhibited doxorubicin (DOX)-induced p53 acetylation and transcription-activation activities by inducing the expression of Sirt1. Knockdown of the Sirt1 expression by the specific siRNA remarkably blocked the inhibitory effects of ISO on DOX-induced p53 acetylation. In addition, we demonstrated that catecholamines induced resistance of cervical cancer cells to chemotherapeutics both in vitro and in vivo and that β2-AR was overexpressed in cervical cancer tissues. Our data suggest that the p53-dependent, chemotherapeutics-induced cytotoxicity in cervical cancer cells may be compromised by catecholamines-induced upregulation of the Sirt1 expression through activating the β2-AR signaling.

References

Oct 24, 2001·Cell·H VaziriR A Weinberg
Apr 15, 2009·The Journal of Cell Biology·Jian YuanZhenkun Lou
Nov 26, 2010·Nature Reviews. Cancer·Daniel Herranz, Manuel Serrano
Oct 25, 2011·Molecular Cell·Hyeog KangJay H Chung
Dec 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·Antje MenssenHeiko Hermeking
Apr 18, 2012·Proceedings of the National Academy of Sciences of the United States of America·Zhaohui FengWenwei Hu
Apr 23, 2013·Oncogene·M Roth, W Y Chen
May 16, 2013·Cancer Metastasis Reviews·Ming ShiNing Guo
Feb 15, 2014·Cell Cycle·Jason M BecktaKristoffer Valerie
Dec 3, 2014·Cancer Treatment Reviews·Michael J DuffyWilliam M Gallagher
Dec 30, 2014·Cancers·Sara M Reed, Dawn E Quelle
Jun 8, 2015·Current Opinion in Hematology·Ling Li, Ravi Bhatia
Aug 25, 2015·Nature Reviews. Cancer·Steven W ColeAnil K Sood
Sep 25, 2015·Expert Review of Anticancer Therapy·Mariateresa LapresaNicoletta Colombo
Oct 28, 2016·Oncogene·S ElabdC Blattner
Nov 7, 2016·Lancet·Ophira GinsburgLesong Conteh

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Citations

Feb 16, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hemn MohammadpourXuefang Cao
Sep 25, 2017·Oncotarget·Hua-Chuan Zheng
May 7, 2019·Journal of Drug Targeting·Bin ZhaoPeng Shang
Jan 5, 2021·Frontiers in Cell and Developmental Biology·Wenjun WangJiuwei Cui
Dec 5, 2020·Critical Reviews in Oncology/hematology·Xiangxuan ZhaoZaiming Lu
Jan 27, 2021·Cancers·Agnete Witness Praest JensenGitte Holmen Olofsson
Dec 19, 2020·Cancer Research·Deborah A SilvermanMoran Amit
Jul 12, 2020·Journal of Neuroimmunology·Boris MravecLubica Horvathova
Apr 14, 2021·Cell Death Discovery·Huan WangGonghui Li
Jul 27, 2021·Frontiers in Cell and Developmental Biology·Guoqiang ChenXiaojun Liu

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Methods Mentioned

BETA
ubiquitination
sumoylation
acetylation
transfection
cofocal microscopy
xenografts

Software Mentioned

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