Aminated Fullerene Abrogates Cancer Cell Migration by Directly Targeting Myosin Heavy Chain 9.

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.