Merkel Cell Polyomavirus Small T Antigen Drives Cell Motility via Rho-GTPase-Induced Filopodium Formation.

Journal of Virology
Gabrielė StakaitytėAdrian Whitehouse

Abstract

Cell motility and migration is a complex, multistep, and multicomponent process intrinsic to progression and metastasis. Motility is dependent on the activities of integrin receptors and Rho family GTPases, resulting in the remodeling of the actin cytoskeleton and formation of various motile actin-based protrusions. Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high likelihood of recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is associated with the majority of MCC cases, and MCPyV-induced tumorigenesis largely depends on the expression of the small tumor antigen (ST). Since the discovery of MCPyV, a number of mechanisms have been suggested to account for replication and tumorigenesis, but to date, little is known about potential links between MCPyV T antigen expression and the metastatic nature of MCC. Previously, we described the action of MCPyV ST on the microtubule network and how it impacts cell motility and migration. Here, we demonstrate that MCPyV ST affects the actin cytoskeleton to promote the formation of filopodia through a mechanism involving the catalytic subunit of protein phosphatase 4 (PP4C). We also show that MCPyV ST-induced cell motility is dependent upon the activities of the R...Continue Reading

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Citations

Feb 21, 2018·The Journal of Biological Chemistry·Gabrielė StakaitytėAdrian Whitehouse
Oct 6, 2018·Nature Reviews. Clinical Oncology·Paul W HarmsUNKNOWN International Workshop on Merkel Cell Carcinoma Research (IWMCC) Working Group
Aug 15, 2019·International Journal of Molecular Sciences·Ugo Moens, Andrew Macdonald
Jul 16, 2020·Cancers·Laura StreitStéphane Gasman
Jul 9, 2020·Cancers·Valeria PietropaoloUgo Moens
Nov 25, 2020·Annual Review of Pathology·James A DeCaprio

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Methods Mentioned

BETA
GTPases
pulldowns
coimmunoprecipitation
pulldown
GTPase
xenograft
transfections

Software Mentioned

IncuCyte
Image J
ImageJ

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