Merkel cell polyomavirus large T antigen is detected in rare cases of nonmelanoma skin cancer

2013 ◽  
Vol 40 (6) ◽  
pp. 543-549 ◽  
Author(s):  
Kirsten D. Mertz ◽  
Aino Paasinen ◽  
Andreas Arnold ◽  
Michèle Baumann ◽  
Felix Offner ◽  
...  
Keyword(s):  
Skin Cancer ◽  
T Antigen ◽  
Nonmelanoma Skin Cancer ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Large T Antigen

scholarly journals Merkel Cell Polyomavirus Large T Antigen Disrupts Lysosome Clustering by Translocating Human Vam6p from the Cytoplasm to the Nucleus

2011 ◽  
Vol 286 (19) ◽  
pp. 17079-17090 ◽  
Author(s):  
Xi Liu ◽  
Jennifer Hein ◽  
Simon C. W. Richardson ◽  
Per H. Basse ◽  
Tuna Toptan ◽  
...  
Keyword(s):  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Large T Antigen

Molecular prevalence of Merkel cell polyomavirus in nonmelanoma skin cancer in a Brazilian population

2017 ◽  
Vol 42 (4) ◽  
pp. 390-394 ◽  
Author(s):  
T. R. Bellott ◽  
C. F. Baez ◽  
S. G. Almeida ◽  
M. T. Venceslau ◽  
M. G. Zalis ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Nonmelanoma Skin Cancer ◽  
Merkel Cell Polyomavirus ◽  
Brazilian Population ◽  
Merkel Cell

scholarly journals Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication

Cancers ◽  
2014 ◽  
Vol 6 (3) ◽  
pp. 1464-1486 ◽  
Author(s):  
Jason Diaz ◽  
Xin Wang ◽  
Sabrina Tsang ◽  
Jing Jiao ◽  
Jianxin You
Keyword(s):  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Large T Antigen

Significant overexpression of the Merkel cell polyomavirus (MCPyV) large T antigen in Merkel cell carcinoma

Head & Neck ◽  
2012 ◽  
Vol 35 (2) ◽  
pp. 184-189 ◽  
Author(s):  
Boban M. Erovic ◽  
Ayman Al Habeeb ◽  
Luke Harris ◽  
David P. Goldstein ◽  
Danny Ghazarian ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Large T Antigen

scholarly journals Genetic and Structural Analysis of Merkel Cell Polyomavirus Large T Antigen from Diverse Biological Samples

Intervirology ◽  
2014 ◽  
Vol 57 (6) ◽  
pp. 331-336 ◽  
Author(s):  
Camila Freze Baez ◽  
Nuria Cirauqui Diaz ◽  
Silvia Maria Baeta Cavalcanti ◽  
Rafael Brandão Varella
Keyword(s):  
Structural Analysis ◽  
Biological Samples ◽  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Large T Antigen

scholarly journals Merkel Cell Polyomavirus Small T Antigen Mediates Microtubule Destabilization To Promote Cell Motility and Migration

2014 ◽  
Vol 89 (1) ◽  
pp. 35-47 ◽  
Author(s):  
Laura M. Knight ◽  
Gabriele Stakaityte ◽  
Jennifer, J. Wood ◽  
Hussein Abdul-Sada ◽  
David A. Griffiths ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Cell Motility ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Tumor Antigen ◽  
Molecular Mechanisms ◽  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Potential Link

ABSTRACTMerkel cell carcinoma (MCC) is an aggressive skin cancer of neuroendocrine origin with a high propensity for recurrence and metastasis. Merkel cell polyomavirus (MCPyV) causes the majority of MCC cases due to the expression of the MCPyV small and large tumor antigens (ST and LT, respectively). Although a number of molecular mechanisms have been attributed to MCPyV tumor antigen-mediated cellular transformation or replication, to date, no studies have investigated any potential link between MCPyV T antigen expression and the highly metastatic nature of MCC. Here we use a quantitative proteomic approach to show that MCPyV ST promotes differential expression of cellular proteins implicated in microtubule-associated cytoskeletal organization and dynamics. Intriguingly, we demonstrate that MCPyV ST expression promotes microtubule destabilization, leading to a motile and migratory phenotype. We further highlight the essential role of the microtubule-associated protein stathmin in MCPyV ST-mediated microtubule destabilization and cell motility and implicate the cellular phosphatase catalytic subunit protein phosphatase 4C (PP4C) in the regulation of this process. These findings suggest a possible molecular mechanism for the highly metastatic phenotype associated with MCC.IMPORTANCEMerkel cell polyomavirus (MCPyV) causes the majority of cases of Merkel cell carcinoma (MCC), an aggressive skin cancer with a high metastatic potential. However, the molecular mechanisms leading to virally induced cancer development have yet to be fully elucidated. In particular, no studies have investigated any potential link between the virus and the highly metastatic nature of MCC. We demonstrate that the MCPyV small tumor antigen (ST) promotes the destabilization of the host cell microtubule network, which leads to a more motile and migratory cell phenotype. 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.

scholarly journals Strategy for eliciting antigen-specific CD8+ T cell-mediated immune response against a cryptic CTL epitope of merkel cell polyomavirus large T antigen

2012 ◽  
Vol 2 (1) ◽  
pp. 36 ◽  
Author(s):  
Bianca P Gomez ◽  
Connie Wang ◽  
Raphael P Viscidi ◽  
Shiwen Peng ◽  
Liangmei He ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cd8 T Cell ◽  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Large T Antigen ◽  
Ctl Epitope ◽  
Cell Mediated Immune Response

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

2017 ◽  
Vol 92 (2) ◽  
Author(s):  
Gabrielė Stakaitytė ◽  
Nnenna Nwogu ◽  
Samuel J. Dobson ◽  
Laura M. Knight ◽  
Christopher W. Wasson ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Actin Cytoskeleton ◽  
Cell Motility ◽  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Rho Family Gtpases ◽  
Tumor Virus ◽  
Rho Family ◽  
And Migration

ABSTRACTCell 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 Rho family GTPases Cdc42 and RhoA. In addition, our results indicate that the MCPyV ST-PP4C interaction results in the dephosphorylation of β1integrin, likely driving the cell motility pathway. These findings describe a novel mechanism by which a tumor virus induces cell motility, which may ultimately lead to cancer metastasis, and provides opportunities and strategies for targeted interventions for disseminated MCC.IMPORTANCEMerkel cell polyomavirus (MCPyV) is the most recently discovered human tumor virus. It causes the majority of cases of Merkel cell carcinoma (MCC), an aggressive skin cancer. However, the molecular mechanisms implicating MCPyV-encoded proteins in cancer development are yet to be fully elucidated. This study builds upon our previous observations, which demonstrated that the MCPyV ST antigen enhances cell motility, providing a potential link between MCPyV protein expression and the highly metastatic nature of MCC. Here, we show that MCPyV ST remodels the actin cytoskeleton, promoting the formation of filopodia, which is essential for MCPyV ST-induced cell motility, and we also implicate the activity of specific Rho family GTPases, Cdc42 and RhoA, in these processes. Moreover, we describe a novel mechanism for the activation of Rho-GTPases and the cell motility pathway due to the interaction between MCPyV ST and the cellular phosphatase catalytic subunit PP4C, which leads to the specific dephosphorylation of β1 integrin. These findings may therefore provide novel strategies for therapeutic intervention for disseminated MCC.

scholarly journals Merkel Cell Polyomavirus Infection, Large T Antigen, Retinoblastoma Protein and Outcome in Merkel Cell Carcinoma

2011 ◽  
Vol 17 (14) ◽  
pp. 4806-4813 ◽  
Author(s):  
Harri Sihto ◽  
Heli Kukko ◽  
Virve Koljonen ◽  
Risto Sankila ◽  
Tom Böhling ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Retinoblastoma Protein ◽  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Large T Antigen
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