title: Biphasic activation of extracellular signal-regulated kinase (ERK) 1/2 in epidermal growth factor (EGF)-stimulated SW480 colorectal cancer cells.
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. [BMB Reports 2016; 49(4): 220-225].
authors.affiliation: Department of Agricultural Biotechnology and Center for Agricultural Biomaterials; Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea.
authors.forename: Donghyun
authors.initials: D
authors.lastname: Joo
authors.affiliation: Department of Agricultural Biotechnology and Center for Agricultural Biomaterials; Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea.
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Woo
authors.affiliation: 2Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Cho
authors.affiliation: Department of Oral Microbiology and Immunology, Dental Research Institute, and BK21 Program, School of Dentistry, Seoul National University, Seoul 08826, Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Han
authors.affiliation: National Research Foundation of Korea, Daejeon 34113, Korea.
authors.forename: Tae Sun
authors.initials: TS
authors.lastname: Min
authors.affiliation: Korean Ginseng Center and Ginseng Genetic Resource Bank, Kyung Hee University, Yongin 17104, Korea.
authors.forename: Deok-Chun
authors.initials: DC
authors.lastname: Yang
authors.affiliation: Department of Agricultural Biotechnology and Center for Agricultural Biomaterials; Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016209:Interleukin-8; D004815:Epidermal Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3