Merkel cell polyomavirus small T antigen mediates microtubule destabilization to promote cell motility and migration.
Bottom Line: These findings suggest a possible molecular mechanism for the highly metastatic phenotype associated with MCC.We further show that MCPyV ST induces this process by regulating the phosphorylation status of the cellular microtubule-associated protein stathmin by its known association with the cellular phosphatase catalytic subunit PP4C.These findings highlight stathmin as a possible biomarker of MCC and as a target for novel antitumoral therapies.
Affiliation: School of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom.Show MeSH
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Mentions: To analyze the effect of MCPyV ST expression on the cellular proteome, SILAC-based quantitative proteomics was performed utilizing a 293 Flp-In cell line capable of inducible MCPyV ST expression, termed i293-ST (15). The i293-ST line is a robust model for this analysis, as inducible levels of MCPyV ST are representative of ST expression in an MCPyV-positive MCC cell line, MKL-1 (Fig. 1A). Bioinformatic analysis using the Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.7 (51) highlighted that a significant proportion of the highly differentially expressed proteins were implicated in gene ontology groupings involving microtubule-associated cytoskeletal organization and dynamics (see Fig. S1 in the supplemental material), which is the focus of this study. Figure S2 in the supplemental material summarizes the differential expression of proteins associated with other gene ontology groupings.
Affiliation: School of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom.