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Inhibition of integrin-linked kinase expression by emodin through crosstalk of AMPKα and ERK1/2 signaling and reciprocal interplay of Sp1 and c-Jun.
Cell Signal. 2015 Jul; 27(7):1469-77.CS

Abstract

Despite the anti-cancer effect of emodin observed in several cancers, the underlying molecular mechanism remains to be elucidated. In this study, we showed that emodin-inhibited NSCLC cell growth and increased phosphorylation of AMPKα and ERK1/2. In addition, emodin-inhibited ILK protein expression. The overexpression of ILK reversed the effect of emodin on cell growth inhibition. Furthermore, the blockade of AMPK by compound C abrogated, while metformin, an activator of AMPK, strengthened the effect of emodin on the inhibition of ILK expression. Interestingly, the inhibitor of MAPK extracellular signaling-regulated kinase (ERK) kinase (MEK)/ERK1/2 (PD98059) attenuated emodin-induced phosphorylation of AMPKα. Moreover, emodin reduced the protein expression of Sp1 and AP-1 subunit c-Jun. Exogenous expression of Sp1 and c-Jun diminished emodin-reduced ILK protein expression. Emodin suppressed ILK promoter activity, which was not observed in cells overexpression of Sp1 and treated with compound C. Intriguingly, exogenous expression of c-Jun overcame the emodin-inhibited Sp1 protein expression. Collectively, our results demonstrate that emodin inhibits ILK expression through AMPKα-mediated reduction of Sp1 and c-Jun. Metformin enhances the effects of emodin. Exogenous expression of Sp1 and c-Jun resists emodin-inhibited ILK promoter activity and protein expression. In addition, the overexpression of c-Jun diminishes emodin-induced AMPKα signaling. Thus, the crosstalk of AMPKα and MEK/ERK1/2 signaling and the reciprocal interaction between Sp1 and c-Jun proteins contribute to the overall responses of emodin. This novel signaling axis may be a therapeutic potential for prevention and treatment of NSCLC.

Authors+Show Affiliations

Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China.Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China.Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China.Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China.Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China.Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China.Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China. Electronic address: swhan20010@live.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25889897

Citation

Tang, Qing, et al. "Inhibition of Integrin-linked Kinase Expression By Emodin Through Crosstalk of AMPKα and ERK1/2 Signaling and Reciprocal Interplay of Sp1 and C-Jun." Cellular Signalling, vol. 27, no. 7, 2015, pp. 1469-77.
Tang Q, Zhao S, Wu J, et al. Inhibition of integrin-linked kinase expression by emodin through crosstalk of AMPKα and ERK1/2 signaling and reciprocal interplay of Sp1 and c-Jun. Cell Signal. 2015;27(7):1469-77.
Tang, Q., Zhao, S., Wu, J., Zheng, F., Yang, L., Hu, J., & Hann, S. S. (2015). Inhibition of integrin-linked kinase expression by emodin through crosstalk of AMPKα and ERK1/2 signaling and reciprocal interplay of Sp1 and c-Jun. Cellular Signalling, 27(7), 1469-77. https://doi.org/10.1016/j.cellsig.2015.04.005
Tang Q, et al. Inhibition of Integrin-linked Kinase Expression By Emodin Through Crosstalk of AMPKα and ERK1/2 Signaling and Reciprocal Interplay of Sp1 and C-Jun. Cell Signal. 2015;27(7):1469-77. PubMed PMID: 25889897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of integrin-linked kinase expression by emodin through crosstalk of AMPKα and ERK1/2 signaling and reciprocal interplay of Sp1 and c-Jun. AU - Tang,Qing, AU - Zhao,Shunyu, AU - Wu,Jingjing, AU - Zheng,Fang, AU - Yang,LiJun, AU - Hu,JingHeng, AU - Hann,Swei Sunny, Y1 - 2015/04/16/ PY - 2015/03/12/received PY - 2015/04/04/revised PY - 2015/04/09/accepted PY - 2015/4/19/entrez PY - 2015/4/19/pubmed PY - 2016/2/18/medline KW - AMPKα KW - Emodin KW - ILK KW - NSCLC KW - Sp1 KW - c-Jun SP - 1469 EP - 77 JF - Cellular signalling JO - Cell Signal VL - 27 IS - 7 N2 - Despite the anti-cancer effect of emodin observed in several cancers, the underlying molecular mechanism remains to be elucidated. In this study, we showed that emodin-inhibited NSCLC cell growth and increased phosphorylation of AMPKα and ERK1/2. In addition, emodin-inhibited ILK protein expression. The overexpression of ILK reversed the effect of emodin on cell growth inhibition. Furthermore, the blockade of AMPK by compound C abrogated, while metformin, an activator of AMPK, strengthened the effect of emodin on the inhibition of ILK expression. Interestingly, the inhibitor of MAPK extracellular signaling-regulated kinase (ERK) kinase (MEK)/ERK1/2 (PD98059) attenuated emodin-induced phosphorylation of AMPKα. Moreover, emodin reduced the protein expression of Sp1 and AP-1 subunit c-Jun. Exogenous expression of Sp1 and c-Jun diminished emodin-reduced ILK protein expression. Emodin suppressed ILK promoter activity, which was not observed in cells overexpression of Sp1 and treated with compound C. Intriguingly, exogenous expression of c-Jun overcame the emodin-inhibited Sp1 protein expression. Collectively, our results demonstrate that emodin inhibits ILK expression through AMPKα-mediated reduction of Sp1 and c-Jun. Metformin enhances the effects of emodin. Exogenous expression of Sp1 and c-Jun resists emodin-inhibited ILK promoter activity and protein expression. In addition, the overexpression of c-Jun diminishes emodin-induced AMPKα signaling. Thus, the crosstalk of AMPKα and MEK/ERK1/2 signaling and the reciprocal interaction between Sp1 and c-Jun proteins contribute to the overall responses of emodin. This novel signaling axis may be a therapeutic potential for prevention and treatment of NSCLC. SN - 1873-3913 UR - https://www.unboundmedicine.com/medline/citation/25889897/Inhibition_of_integrin_linked_kinase_expression_by_emodin_through_crosstalk_of_AMPKα_and_ERK1/2_signaling_and_reciprocal_interplay_of_Sp1_and_c_Jun_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898-6568(15)00131-X DB - PRIME DP - Unbound Medicine ER -