Biphasic activation of extracellular signal-regulated kinase (ERK) 1/2 in epidermal growth factor (EGF)-stimulated SW480 colorectal cancer cells

• Published in: BMB reports Vol. 49; no. 4; pp. 220 - 225
• Main Authors: Joo, Donghyun, Woo, Jong Soo, Cho, Kwang-Hyun, Han, Seung Hyun, Min, Tae Sun, Yang, Deok-Chun, Yun, Cheol-Heui
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 01.04.2016; 생화학분자생물학회
• Subjects: Apoptosis - drug effects; Caspase 3 - metabolism; Cell Line, Tumor; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - pathology; Enzyme Activation - drug effects; Epidermal Growth Factor - pharmacology; Humans; Interleukin-8 - metabolism; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Phosphorylation - drug effects; Protein Transport - drug effects; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2016.49.4.004

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. [BMB Reports 2016; 49(4): 220-225].