HuR translocation to the cytoplasm of cancer cells in actin-independent manner
- Department of Oral Pathology and Biology, Hokkaido University Faculty of Dental Medicine and Graduate School of Dental Medicine, Sapporo (Japan)
- Department of Oral Diagnosis and Medicine, Hokkaido University Faculty of Dental Medicine and Graduate School of Dental Medicine, Sapporo (Japan)
- Department of Restorative Dentistry, Hokkaido University Faculty of Dental Medicine and Graduate School of Dental Medicine, Sapporo (Japan)
Highlights: • Molecular transport system of HuR could be different in individual cancer. • Cancer cells show alternative HuR transport when cytoskeleton structure is impaired. • Oral and cervical cancer implicate a microfilament independent HuR transport. Human antigen R (HuR) is a RNA-binding protein, which binds to the AU-rich element (ARE) in the 3′-untranslated region (3′-UTR) of certain mRNA and is involved in the export and stabilization of ARE-mRNA. HuR constitutively relocates to the cytoplasm in many cancer cells, however the mechanism of intracellular HuR trafficking is poorly understood. To address this question, we examined the functional role of the cytoskeleton in HuR relocalization. We tested the effect of actin depolymerizing macrolide latrunculin A or myosin II ATPase activity inhibitor blebbistatin for HuR relocalization induced by the vasoactive hormone Angiotensin II in cancer and control normal cells. Western blot and confocal imaging data revealed that both inhibitors attenuated the cytoplasmic HuR in normal cells but no such alteration was observed in cancer cells. Concomitant with changes in intracellular HuR localization, both inhibitors markedly decreased the accumulation and half-lives of HuR target ARE-mRNAs in normal cells, whereas no change was observed in cancer cells. Furthermore, co-immunoprecipitation experiments with HuR proteins revealed clear physical interaction with ß-actin only in normal cells. The current study is the first to verify that cancer cells can implicate a microfilament independent HuR transport. We hypothesized that when cytoskeleton structure is impaired, cancer cells can acquire an alternative HuR trafficking strategy.
- OSTI ID:
- 23082686
- Journal Information:
- Experimental Cell Research, Vol. 369, Issue 2; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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