Substrate Stiffness Influences Doxorubicin-Induced p53 Activation via ROCK2 Expression
Joint Authors
Hirata, Hiroaki
Kawauchi, Keiko
Ebata, Takahiro
Mitsui, Yasumasa
Sugimoto, Wataru
Maeda, Miho
Araki, Keigo
Machiyama, Hiroaki
Harada, Ichiro
Sawada, Yasuhiro
Fujita, Hideaki
Source
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-01-16
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
The physical properties of the extracellular matrix (ECM), such as stiffness, are involved in the determination of the characteristics of cancer cells, including chemotherapy sensitivity.
Resistance to chemotherapy is often linked to dysfunction of tumor suppressor p53; however, it remains elusive whether the ECM microenvironment interferes with p53 activation in cancer cells.
Here, we show that, in MCF-7 breast cancer cells, extracellular stiffness influences p53 activation induced by the antitumor drug doxorubicin.
Cell growth inhibition by doxorubicin was increased in response to ECM rigidity in a p53-dependent manner.
The expression of Rho-associated coiled coil-containing protein kinase (ROCK) 2, which induces the activation of myosin II, was significantly higher when cells were cultured on stiffer ECM substrates.
Knockdown of ROCK2 expression or pharmacological inhibition of ROCK decreased doxorubicin-induced p53 activation.
Our results suggest that a soft ECM causes downregulation of ROCK2 expression, which drives resistance to chemotherapy by repressing p53 activation.
American Psychological Association (APA)
Ebata, Takahiro& Mitsui, Yasumasa& Sugimoto, Wataru& Maeda, Miho& Araki, Keigo& Machiyama, Hiroaki…[et al.]. 2017. Substrate Stiffness Influences Doxorubicin-Induced p53 Activation via ROCK2 Expression. BioMed Research International،Vol. 2017, no. 2017, pp.1-10.
https://search.emarefa.net/detail/BIM-1137459
Modern Language Association (MLA)
Ebata, Takahiro…[et al.]. Substrate Stiffness Influences Doxorubicin-Induced p53 Activation via ROCK2 Expression. BioMed Research International No. 2017 (2017), pp.1-10.
https://search.emarefa.net/detail/BIM-1137459
American Medical Association (AMA)
Ebata, Takahiro& Mitsui, Yasumasa& Sugimoto, Wataru& Maeda, Miho& Araki, Keigo& Machiyama, Hiroaki…[et al.]. Substrate Stiffness Influences Doxorubicin-Induced p53 Activation via ROCK2 Expression. BioMed Research International. 2017. Vol. 2017, no. 2017, pp.1-10.
https://search.emarefa.net/detail/BIM-1137459
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1137459