DOI: 10.1073/pnas.0305855101. Illegitimate WNT signaling promotes proliferation of multiple myeloma cells

Illegitimate WNT signaling promotes proliferation of multiple myeloma cells

10.1073/pnas.0305855101

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The unrestrained growth of tumor cells is generally attributed to mutations in essential growth control genes, but tumor cells are also influenced by signals from the environment. In multiple myeloma (MM), the factors and signals coming from the bone marrow microenvironment are possibly even essential for the growth of the tumor cells. As targets for intervention, these signals may be equally important as mutated oncogenes. Given their oncogenic potential, WNT signals form a class of paracrine growth factors that could act to influence MM cell growth. In this paper, we report that MM cells have hallmarks of active WNT signaling, whereas the cells have not undergone detectable mutations in WNT signaling genes such asadenomatous polyposis coliand β-catenin(CTNNB1). We show that the malignant MM plasma cells overexpress β-catenin, including its N-terminally unphosphorylated form, suggesting active β-catenin/T cell factor-mediated transcription. Further accumulation and nuclear localization of β-catenin, and/or increased cell proliferation, was achieved by stimulation of WNT signaling with either Wnt3a, LiCl, or the constitutively active S33Y mutant of β-catenin. In contrast, by blocking WNT signaling by dominant-negative T cell factor, we can interfere with the growth of MM cells. We therefore suggest that MM cells are dependent on an active WNT signal, which may have important implications for the management of this incurable form of cancer.

Bibliography

Derksen, P. W. B., Tjin, E., Meijer, H. P., Klok, M. D., Mac Gillavry, H. D., van Oers, M. H. J., Lokhorst, H. M., Bloem, A. C., Clevers, H., Nusse, R., van der Neut, R., Spaargaren, M., & Pals, S. T. (2004). Illegitimate WNT signaling promotes proliferation of multiple myeloma cells. Proceedings of the National Academy of Sciences, 101(16), 6122â6127.

Authors 13

Patrick W. B. Derksen (first)
Esther Tjin (additional)
Helen P. Meijer (additional)
Melanie D. Klok (additional)
Harold D. Mac Gillavry (additional)
Marinus H. J. van Oers (additional)
Henk M. Lokhorst (additional)
Andries C. Bloem (additional)
Hans Clevers (additional)
Roel Nusse (additional)
Ronald van der Neut (additional)
Marcel Spaargaren (additional)
Steven T. Pals (additional)

References 48 Referenced 256

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Dates

Type	When
Created	21 years, 4 months ago (April 5, 2004, 8:54 p.m.)
Deposited	2 years, 4 months ago (April 28, 2023, 2:46 a.m.)
Indexed	5 minutes ago (Sept. 3, 2025, 6:48 a.m.)
Issued	21 years, 4 months ago (April 5, 2004)
Published	21 years, 4 months ago (April 5, 2004)
Published Online	21 years, 4 months ago (April 5, 2004)
Published Print	21 years, 4 months ago (April 20, 2004)

Funders 0

None

BibTeX

@article{Derksen_2004, title={Illegitimate WNT signaling promotes proliferation of multiple myeloma cells}, volume={101}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0305855101}, DOI={10.1073/pnas.0305855101}, number={16}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Derksen, Patrick W. B. and Tjin, Esther and Meijer, Helen P. and Klok, Melanie D. and Mac Gillavry, Harold D. and van Oers, Marinus H. J. and Lokhorst, Henk M. and Bloem, Andries C. and Clevers, Hans and Nusse, Roel and van der Neut, Ronald and Spaargaren, Marcel and Pals, Steven T.}, year={2004}, month=apr, pages={6122–6127} }

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