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Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1 pathway

Oncogene volume 26, pages 7240–7250 (2007)Cite this article

Abstract

Endoglin is a transforming growth factor β (TGFβ) superfamily auxiliary receptor. We had previously shown that it suppressed prostate cancer (PCa) cell motility, and that its expression was lost during PCa progression. The mechanism by which endoglin inhibits PCa cell motility is unknown. Here we demonstrate that endoglin abrogates TGFβ-mediated cell motility, but does not alter cell surface binding of TGFβ. By measuring Smad-specific phosphorylation and Smad-responsive promoter activity, endoglin was shown to constitutively activate Smad1, with little-to-no effect upon Smad3. Knockdown of Smad1 increased motility and abrogated endoglin's effects. As type I activin receptor-like kinases (ALKs) are necessary for Smad activation, we went on to show that knockdown of ALK2, but not TGFβRI (ALK5), abrogated endoglin-mediated decreases in cell motility and constitutively active ALK2 was sufficient to restore a low-motility phenotype in endoglin deficient cells. These findings provide the first evidence that endoglin decreases PCa cell motility through activation of the ALK2-Smad1 pathway.

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Acknowledgements

We express our gratitude to Dr Shan Chen for her many helpful suggestions throughout the manuscript's preparation. This work was funded by the following grants to Raymond C Bergan: a merit review award from the Veterans Administration and a Specialized Program of Research Excellence (SPORE) grant CA90386, from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. Clarissa S Craft was funded by a training grant, T32CA09560, from the National Institutes of Health.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Northwestern University Medical School, Northwestern University and the Robert H Lurie Cancer Center of Northwestern University, Chicago, IL, USA

    C S Craft & R C Bergan

  2. Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA

    D Romero & C P H Vary

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  1. C S Craft
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  2. D Romero
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Correspondence to R C Bergan.

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Supplementary Information accompanies the paper on the Oncogene Web site (http://www.nature.com/onc).

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Craft, C., Romero, D., Vary, C. et al. Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1 pathway. Oncogene 26, 7240–7250 (2007). https://doi.org/10.1038/sj.onc.1210533

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