Aminated Fullerene Abrogates Cancer Cell Migration by Directly Targeting Myosin Heavy Chain 9
| Autor: | Yang Yang, Yang Liu, Mingming Zhen, Jiawei Huo, Jie Li, Shumu Li, Jiao Li, Wei Zhou, Xiaoyan Zhang, Chunru Wang, Jianan Liu, Xiaohong Fang, Haijun Ma, Chong Zhao |
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| Rok vydání: | 2020 |
| Předmět: |
Epithelial-Mesenchymal Transition
Materials science Myosin Heavy Chains Cell Biotin Motility Antineoplastic Agents Cell migration medicine.disease Metastasis Cell biology medicine.anatomical_structure A549 Cells Cell Movement Cell Mobility Biological target Cytoplasm Myosin medicine Humans General Materials Science Fullerenes Drug Screening Assays Antitumor Fluorescein-5-isothiocyanate Protein Binding |
| Zdroj: | ACS Applied Materials & Interfaces. 12:56862-56873 |
| ISSN: | 1944-8252 1944-8244 |
| Popis: | Functional fullerene derivatives exhibit fantastic inhibitory capabilities against cancer survival and metastasis, but the absence of clarified biological molecular targets and ambiguous regulation mechanisms set barriers for their clinical transformation. Cancer metastasis is the primary cause of mortality and initiated with increased cell migration, making cell motility regulation a high-value therapeutic target in precision medicine. Herein, a critical molecular target of the aminated fullerene derivative (C70-EDA), myosin heavy chain 9 (MYH9), was initially identified by a pull-down assay and MS screening. MYH9 is a cytoplasm-located protein and is responsible for cell motility and epithelial-mesenchymal transition regulation. Omics data from large-scale clinical samples reveals that MYH9 gets overexpressed in various cancers and correlates with unfavorable prognosis, indicating that it is a potential antineoplastic target. It is unveiled that C70-EDA binds to the C-terminal of MYH9, triggering the transport of MYH9 from the cytoplasm to the cell edge, blocking the MYH9-involved cell mobility, and inhibiting the metastasis-associated EMT process. This work provides a precise biological target and new strategies for fullerene applications in cancer therapy. |
| Databáze: | OpenAIRE |
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