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Aminated Fullerene Abrogates Cancer Cell Migration by Directly Targeting Myosin Heavy Chain 9
Wei Zhou1, Jiawei Huo1,2, Yang Yang1
1Beijing National Research Center for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Science, Beijing 100190, China.
Abstract:
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.
Insights
Aminated fullerene derivative C70-EDA targets myosin heavy chain 9 (MYH9), a protein overexpressed in cancers. This discovery offers new strategies for fullerene-based cancer therapy by inhibiting metastasis.
Area of Science:
- Nanomedicine
- Cancer Biology
- Molecular Therapeutics
Background:
- Functional fullerene derivatives show promise in inhibiting cancer survival and metastasis.
- Lack of identified molecular targets and regulatory mechanisms hinders clinical translation of fullerenes.
- Cancer metastasis, driven by cell migration, presents a critical therapeutic target.
Purpose of the Study:
- To identify a molecular target for the aminated fullerene derivative (C70-EDA).
- To elucidate the mechanism by which C70-EDA inhibits cancer metastasis.
- To explore fullerene derivatives as potential antineoplastic agents.
Main Methods:
- Pull-down assay and mass spectrometry (MS) screening to identify molecular targets.
- Analysis of omics data from large-scale clinical samples.
- Investigation of C70-EDA binding to myosin heavy chain 9 (MYH9) and its downstream effects.
Main Results:
- Myosin heavy chain 9 (MYH9) identified as a direct molecular target of C70-EDA.
- MYH9 is overexpressed in various cancers and correlates with poor prognosis.
- C70-EDA binding to MYH9 inhibits cell motility and metastasis-associated epithelial-mesenchymal transition (EMT).
Conclusions:
- MYH9 is a validated antineoplastic target for fullerene-based cancer therapy.
- C70-EDA effectively inhibits cancer cell migration and metastasis by modulating MYH9.
- This study provides a precise molecular target and novel strategies for fullerene applications in oncology.
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