Selective [beta]2-AR Blockage Suppresses Colorectal Cancer Growth Through Regulation of EGFR-Akt/ERK1/2 Signaling, G1-Phase Arrest, and Apoptosis

The stress-upregulated catecholamines-activated [beta]1- and [beta]2-adrenergic receptors ([beta]1/2-ARs) have been shown to accelerate the progression of cancers such as colorectal cancer (CRC). We investigated the underlying mechanism of the inhibition of [beta]1/2-ARs signaling for the treatment...

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Published in:Journal of cellular physiology 2016-02, Vol.231 (2), p.459
Main Authors: Chin, Chih-Chien, Li, Jhy-Ming, Lee, Kam-Fai, Huang, Yun-Ching, Wang, Kuan-Chieh, Lai, Hsiao-Ching, Cheng, Chih-Chung, Kuo, Yi-Hung, Shi, Chung-Sheng
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Language:English
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Summary:The stress-upregulated catecholamines-activated [beta]1- and [beta]2-adrenergic receptors ([beta]1/2-ARs) have been shown to accelerate the progression of cancers such as colorectal cancer (CRC). We investigated the underlying mechanism of the inhibition of [beta]1/2-ARs signaling for the treatment of CRC and elucidated the significance of [beta]2-AR expression in CRC in vitro and in clinical samples. The impacts of [beta]1/2-AR antagonists in CRC in vitro and CRC-xenograft in vivo were examined. We found that repression of [beta]2-AR but not [beta]1-AR signaling selectively suppressed cell viability, induced G1-phase cell cycle arrest, caused both intrinsic and extrinsic pathways-mediated apoptosis of specific CRC cells and inhibited CRC-xenograft growth in vivo. Moreover, the expression of [beta]2-AR was not consistent with the progression of CRC in vitro or in clinical samples. Our data evidence that the expression profiles, signaling, and blockage of [beta]2-AR have a unique pattern in CRC comparing to other cancers. [beta]2-AR antagonism selectively suppresses the growth of CRC accompanying active [beta]2-AR signaling, which potentially carries wild-type KRAS, in vitro and in vivo via the inhibition of [beta]2-AR transactivated EFGR-Akt/ERK1/2 signaling pathway. Thus, [beta]2-AR blockage might be a potential therapeutic strategy for combating the progressions of [beta]2-AR-dependent CRC. J. Cell. Physiol. 231: 459-472, 2016. © 2015 Wiley Periodicals, Inc.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.25092