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9 results on '"Frank, Brittany P."'

4. Loss Of Klotho During Melanoma Progression Leads To Increased Filamin Cleavage, Increased Wnt5A Expression and Enhanced Melanoma Cell Motility

Author

Camilli, Tura C., Xu, Mai, O'Connell, Michael P., Chien, Bonnie, Frank, Brittany P., Subaran, Sarah, Indig, Fred E., Morin, Patrice J., Hewitt, Stephen M., and Weeraratna, Ashani T.

Subjects
Filamins, Microfilament Proteins, urologic and male genital diseases, Article, Wnt-5a Protein, body regions, Gene Expression Regulation, Neoplastic, Wnt Proteins, Mice, Contractile Proteins, Cell Movement, Cell Line, Tumor, Proto-Oncogene Proteins, embryonic structures, Disease Progression, Animals, Humans, sense organs, Neoplasm Metastasis, Klotho Proteins, Melanoma, Heparan Sulfate Proteoglycans, Glucuronidase, Signal Transduction
Abstract

We have previously shown that Wnt5A-mediated signaling can promote melanoma metastasis. It has been shown that Wnt signaling is antagonized by the protein Klotho, which has been implicated in aging. We show here that in melanoma cells, expressions of Wnt5A and Klotho are inversely correlated. In the presence of recombinant Klotho (rKlotho), we show that Wnt5A internalization and signaling is decreased in high Wnt5A-expressing cells. Moreover, in the presence of rKlotho, we observe an increase in Wnt5A remaining in the medium, coincident with an increase in sialidase activity, and decrease in syndecan expression. These effects can be inhibited using a sialidase inhibitor. In addition to its effects on Wnt5A internalization, we also demonstrate that Klotho decreases melanoma cell invasive potential by a second mechanism that involves the inhibition of calpain and a resultant decrease in filamin cleavage, which we demonstrate is critical for melanoma cell motility.

Published
2010

7. Wnt5A Activates the Calpain-Mediated Cleavage of Filamin A

Author

O'Connell, Michael P., primary, Fiori, Jennifer L., additional, Baugher, Katherine M., additional, Indig, Fred E., additional, French, Amanda D., additional, Camilli, Tura C., additional, Frank, Brittany P., additional, Earley, Rachel, additional, Hoek, Keith S., additional, Hasskamp, Joanne H., additional, George Elias, E., additional, Taub, Dennis D., additional, Bernier, Michel, additional, and Weeraratna, Ashani T., additional

Published
2009
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9. Heparan Sulfate Proteoglycan Modulation of Wnt5A Signal Transduction in Metastatic Melanoma CelIs.

Author

O'ConneII, Michael P., Fiori, Jennifer L., Kershner, Emily K., Frank, Brittany P., lndig, Fred E., Taub, Dennis D., Hoek, Keith S., and Weeraratna, Ashani T.

Subjects
*PROTEOGLYCANS, *GLYCOSAMINOGLYCANS, *MELANOMA, *CANCER cells, *METASTASIS, *CANCER invasiveness
Abstract

Heparan sulfate proteoglycans (HSPGs) are important modulators for optimizing signal transduction of many pathways, including the Wnt pathways. We demonstrate that HSPG glycosaminoglycan levels increased with increasing metastatic potential of melanoma cells. Previous studies have demonstrated that Wnt5A increases the invasiveness of melanoma cells. We further demonstrate that HSPGs potentiate Wnt5A signaling, since enzymatic removal of the HSPG backbone resulted in a decrease in cellular Wnt5A levels, an increase in secreted Wnt5A in cell media, a decrease in downstream signaling, and ultimately, a decrease in invasiveness. Specifically, syndecan 1 and syndecan 4 expression correlated to Wnt5A expression and melanoma malignancy. Knockdown of syndecan 1 or 4 caused decreases in cell invasion, which could be restored by treating the cells with recombinant Wnt5A. These data indicate that syndecan 1 and 4 correlate to increased metastatic potential in melanoma patients and are an important component of the Wnt5A autocrine signaling loop, the activation of which leads to increased metastasis of melanoma. [ABSTRACT FROM AUTHOR]

Published
2009
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