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Cytokeratin19 induced by HER2/ERK binds and stabilizes HER2 on cell membranes
- Authors
- Ju, J-h; Oh, S.; Lee, K-m; Yang, W.; Nam, K. S.; Moon, H-G; Noh, D-Y; Kim, C. G.; Park, G.; Park, J. B.; Lee, T.; Arteaga, C. L.; Shin, I.
- Issue Date
- Apr-2015
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- Animals; Antibodies; Breast Neoplasms; Cell Line, Tumor; Cell Membrane; Cell Proliferation; Cell Survival; Extracellular Signal-Regulated MAP Kinases; Female; Gene Expression Regulation; HEK293 Cells; Humans
- Citation
- CELL DEATH AND DIFFERENTIATION, v.22, no.4, pp.665 - 676
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL DEATH AND DIFFERENTIATION
- Volume
- 22
- Number
- 4
- Start Page
- 665
- End Page
- 676
- ISSN
- 1350-9047
- Abstract
- Cytokeratin19 (KRT19) is widely used as a biomarker for the detection of disseminated tumors. Using an LC-MS/MS proteomics approach, we found that KRT19 was upregulated in HER2-overexpressing cells and tissues. KRT19 expression was induced by HER2-downstream ERK at the transcriptional level. Another HER2-downstream kinase, Akt, was found to phosphorylate KRT19 on Ser35 and induce membrane translocation of KRT19 and remodeling of KRT19 from filamentous to granulous form. KRT19 phosphorylated by Akt could bind HER2 on the plasma membrane and stabilized HER2 via inhibition of proteasome-mediated degradation of HER2. Silencing of KRT19 by shRNA resulted in increased ubiquitination and destabilization of HER2. Moreover, treatment of KRT19 antibody resulted in downregulation of HER2 and reduced cell viability. These data provide a new rationale for targeting HER2-positive breast cancers.
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Related Researcher
- Kim, Chul Geun
- COLLEGE OF NATURAL SCIENCES (DEPARTMENT OF LIFE SCIENCE)