BMB Rep. 2016; 49(4): 220-225  
Biphasic activation of extracellular signal-regulated kinase (ERK) 1/2 in epidermal growth factor (EGF)-stimulated SW480 colorectal cancer cells
Donghyun Joo1, Jong Soo Woo1, Kwang-Hyun Cho2, Seung Hyun Han3, Tae Sun Min4, Deok-Chun Yang5 & Cheol-Heui Yun1,*
1Department of Agricultural Biotechnology and Center for Agricultural Biomaterials; Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, 2Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, 3Department of Oral Microbiology and Immunology, Dental Research Institute, and BK21 Program, School of Dentistry, Seoul National University, Seoul 08826, 4National Research Foundation of Korea, Daejeon 34113, 5Korean Ginseng Center and Ginseng Genetic Resource Bank, Kyung Hee University, Yongin 17104, Korea
Correspondence to: Tel: +82-2-880-4802; Fax: +82-2-886-4805; E-mail: cyun@snu.ac.kr
Received: January 9, 2016; Revised: February 1, 2016; Accepted: February 11, 2016; Published online: April 30, 2016.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Abstract
Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signalregulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a role in cancer cell survival; thus, regulation of ERK1/2 activation may improve the efficacy of cancer therapies that target ERK signaling.
Keywords: Biphasic activation, Cancer cell survival, ERK pathway, pERK translocation, SW480 cells

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